JP4037433B2 - Chemical analyzer and dispensing method - Google Patents

Description

  The present invention relates to a chemical analyzer and a dispensing method that are excellent in quantification and safety.

In recent years, an integrated chemical and biochemical analysis system called μ-TAS (Micro Total Analysis System), which integrates functional parts such as liquid feeding, mixing, reaction, and analysis on a chip of about several centimeters of glass or silicon. Proposed. FIG. 13 shows one conventional example of μ-TAS. As shown in FIG. 13, in the μ-TAS, a sample channel 51 is formed in a glass chip 80, and mixing, reaction, detection, and the like of a sample (reagent) are performed in the sample channel 51, whereby drug discovery is performed. And preliminary experiments for medical diagnosis. When a sample is injected from the sample injection unit 62, the sample passes through the sample channel 51 and is mixed by the mixing unit 61a. Then, a chemical reaction of the sample occurs in the reaction unit 61b, and the sample after the reaction is separated in the separation unit 61c. The sample after the reaction is detected by the detection unit 61d, and the unnecessary sample is collected by the waste liquid unit 60. Since μ-TAS can greatly reduce the amount of samples and specimens compared to conventional analysis integration systems, it is expected to reduce the throughput time and waste liquid.

  In addition, a microreactor has been proposed in which these device functions are built in a micro space such as a microchip and a plurality of more complex chemical reactions and drug discovery can be performed at once. In these microreactors, it is important to handle a small amount of chemical solution. For example, when dispensing a chemical solution or the like into a micro reaction tank on a chip or spotting, means such as a syringe, an ink jet mechanism, and a spotter are used.

  Handling of chemicals with μ-TAS chips is difficult due to the small amount of liquid, and the amount of liquid decreases due to evaporation or adhesion to the wall, making it difficult to ensure quantitativeness. Had trouble.

  For example, when the same chemical solution is dispensed into a plurality of reaction vessels (such as the sample injection unit 62 in FIG. 13), the chemical solution evaporates, so that the amount of chemical solution in the reaction vessel injected first and finally There is a possibility that the amount of chemicals in the injected reaction tank is different. This can lead to problems in quantification. In addition, when dispensing a plurality of chemical solutions, the mixing ratio of the plurality of chemical solutions may change due to evaporation.

  Furthermore, in the micro PCR device, the chemical solution is dispensed into the container, and then the cover is covered and the inside is heated and cooled. However, the chemical solution evaporates after dispensing, and the amount of the liquid may be smaller than the reaction tank capacity. At this time, if the cover is left as it is, the air layer remains inside the reaction vessel, so that there is a risk that the air will expand and burst when heated.

  Therefore, in the present invention, the sample dispensed in the reaction tank does not evaporate, and the chemical analysis apparatus and dispensing method excellent in quantitative and safety can be sealed without leaving any gas. The purpose is to provide.

  In order to achieve the above object, the first feature of the present invention is (i) a container-like member sandwiched between a first bonding member and a second bonding member, and for injecting a sample. (B) a mounting block having a well for arranging the reaction tank, (c) a third bonding member in contact with the second bonding member, and a third bonding member. The gist of the present invention is a chemical analysis apparatus comprising a sealing lid that seals a surface for injecting a sample of a reaction tank composed of a cover member sandwiched around a fourth adhesive member facing each other. The second bonding member and the third bonding member of the chemical analysis device according to the first feature may be bonded by an adhesive. Further, the second bonding member and the third bonding member of the chemical analyzer according to the first feature may each include a concave portion and a convex portion, and may be coupled by fitting the concave portion and the convex portion. .

  According to the chemical analyzer according to the first feature, the sample dispensed in the reaction vessel does not evaporate, and the reaction vessel can be sealed without leaving a gas. Even a reaction tank and a sealing lid made of a material that is difficult to bond can be easily bonded by the bonding member.

The second feature of the present invention is (a) a container-like member sandwiched between the first bonding member and the second bonding member, and dividing the sample into a reaction vessel for injecting the sample. And (b) the periphery of the reaction vessel was sandwiched between the third bonding member contacting the second bonding member and the fourth bonding member facing the third bonding member. The gist of the present invention is a dispensing method including a step of fitting a sealing lid made of a cover member and (c) a step of placing the reaction tank on the mounting block. The fitting step of the dispensing method according to the second feature may include a step of joining the second bonding member and the third bonding member with an adhesive. In addition, the step of fitting the dispensing method according to the second feature may include a step of fitting by fitting a concave portion and a convex portion respectively provided in the second adhesive member and the third adhesive member. .

  According to the dispensing method according to the second feature, the sample dispensed in the reaction vessel does not evaporate, and the reaction vessel can be sealed without leaving any gas. Even a reaction tank and a sealing lid made of a material that is difficult to bond can be easily bonded by the bonding member.

  ADVANTAGE OF THE INVENTION According to this invention, the chemical analyzer and the dispensing method excellent in the quantitative property and safety | security which can seal the reaction tank, without the sample dispensed in the reaction tank evaporating and leaving no gas Can be provided.

  Next, first to third embodiments of the present invention will be described with reference to the drawings. In the following description of the drawings, the same or similar parts are denoted by the same or similar reference numerals. However, it should be noted that the drawings are schematic.

(First embodiment)
As shown in FIG. 1A, the chemical analysis apparatus according to the first embodiment injects a container-like member 8 in which a reaction tank 5a for injecting a sample is disposed, and a sample of the container-like member 8. A cover member 11 that covers the surface to be heated, a heating / cooling device 7 that keeps the temperature inside the reaction vessel 5a below the freezing point of the sample, and a mounting block 12a that mounts the container-like member 8 via the heating / cooling device 7 With. Here, the volume of the sample to be dispensed is V for the volume of the sample when solidified, V _{1 for} the volume of the reaction vessel 5a, and a (= solid volume / liquid) when the sample is solidified from liquid to solid. Volume), V ₁ ≦ V ≦ a · V ₁ . The volume V when solidified is equal to V ₁ is the time when the volume of the solidified sample is equal to the volume V _{1 of the} reaction vessel 5a. The volume V when solidified is equal to a · V ₁ is the time when the volume of the melted sample is equal to the volume V _{1 of the} reaction vessel 5a.

  The container-like member 8 and the cover member 11 are made of a material such as a flexible resin that is resistant to a chemical reaction such as polypropylene having a thickness of about 10 to 50 μm. For example, it is made of glass epoxy resin, fluorine resin such as polypropylene (PP) or polytetrafluoroethylene (PTFE), glass material such as quartz, semiconductor material such as silicon, metal or the like. Here, examples of the metal include nichrome, hastelloy, mnemonic, inconel, and stainless steel having low thermal conductivity. The mounting block 12 a includes a heating / cooling device 7. As the heating / cooling device 7, a structure in which a Peltier element, a heat pipe, or the like is fed back using a temperature detection element such as a thermocouple can be used.

  FIG.1 (b) is the figure which looked at the chemical analyzer which concerns on 1st Embodiment from the top in the state which removed the cover member 11. FIG. The length L1 of the chemical analyzer is, for example, 10 to 30 mm, and the diameter d of the reaction vessel 5a is preferably 1 μm to 5 mm. Although the diameter may be 5 mm or more, the integration density is lowered and the function as a microreactor is reduced. If the processing technology permits, a diameter d of 1 μm or less is possible, but it is not realistic in terms of operability and analysis sensitivity in mixing, reaction, and analysis. Accordingly, considering the integration density, analysis sensitivity, and ease of manufacture as a microreactor, the thickness may be about 20 μm to 1 mm. More preferably, if the thickness is about 0.1 to 1 mm, the integration density is kept high and the operability is good.

  According to the chemical analyzer according to the first embodiment, the reaction vessel 5a is sealed with the cover member 11 to the solidified sample, so that the sample dispensed in the reaction vessel 5a does not evaporate, and The reaction vessel 5a can be sealed without leaving any gas.

  Next, a method for dispensing using the chemical analyzer according to the first embodiment will be described.

  (A) First, as shown in FIG. 2A, the container-like member 8 is disposed on the mounting block 12 a provided with the heating and cooling device 7. The container-like member 8 has a concave reaction tank 5a. At this time, the heating / cooling device 7 is temperature-controlled to a temperature below the freezing point of the sample. When the liquid sample 10b is injected into the reaction tank 5a from the dispensing needle 6 of the dispensing device 9, the liquid sample 10b is solidified. Here, the dispensing device 9 has an injection needle-like dispensing needle 6 at its tip, and the dispensing needle 6 has an inner diameter of, for example, about 0.1 mm and an outer diameter of about 0.3 mm.

If the diameter of the reaction vessel 5a is about 1 μm, a microcapillary having the same fine structure as that of a probe of a scanning tunneling microscope may be used. The dispensing device 9 may have a structure in which a plurality of dispensing needles 6 are provided in accordance with the reaction tank 5a of the container-like member 8, and a sample is injected into the plurality of reaction tanks 5a by one dispensing. .

(B) When the liquid sample 10b is poured into the reaction vessel 5, the sample is solidified and becomes a solid sample 10a as shown in FIG. 2 (b). The injection rate of the chemical solution needs to be equal to or less than the rate of coagulation. If the injection rate and the coagulation rate are the same, the sample can be injected efficiently. In addition, since the sample may condense when solidified, it is desirable that the atmosphere be dry. Therefore, it is preferable to perform in a rare gas such as nitrogen (N ₂ ) gas, hydrogen (H ₂ ) gas, or helium (He) gas having a low dew point. At this time, the volume when the coagulation of the sample being injected V, V ₁ the volume of the reaction vessel _5a, the expansion rate when solidified from a liquid sample to a solid and a (= solid volume / liquid volume), A sample having a volume satisfying V ₁ ≦ V ≦ a · V ₁ is injected. Accordingly, the upper surface of the solid sample 10a is equal to or higher than the upper surface of the reaction vessel 5a.

(C) Next, as shown in FIG. 2C, the cover member 11 is placed so as to cover the upper surface of the solid sample 10a. The cover member 11 is a flexible material that can be flexibly matched with the shape of the upper surface of the solid sample 10a. For this reason, by adhering the cover member 11 and the container-like member 8, it is possible to prevent air from being mixed into the reaction vessel 5a. In particular, if the cover member 8 is covered with N ₂ gas, H ₂ gas, rare gas or the like using a glove box or a remote control system, mixing of air in the reaction vessel 5a can be prevented. As a method for bonding the container-like member 8 and the cover member 11, heat, ultrasonic vibration, or the like may be used in addition to using an adhesive.

  (D) Next, as shown in FIG. 2 (d), the heating and cooling device 7 is used to heat the temperature to the boiling point or more and the boiling point or less of the sample to melt the sample and return it to the liquid sample 10b. At this time, the volume of the liquid sample 10b is reduced, but the cover member 11 and the container-like member 8 are flexible and can be changed in shape according to the volume of the sample. In 5 a, there is no mixing of air.

  (E) Thereafter, the liquid sample 10b is analyzed. For example, when nucleic acid amplification is performed on the assumption that the liquid sample 10b is nucleic acid (DNA), the liquid sample 10b is heated, the DNA is dissociated at around 95 ° C, annealed at around 55 ° C, and replicated at around 70 ° C. And amplify.

  (F) After the analysis is completed, the container-like member 8 containing the liquid sample 10b is removed from the mounting block 12a. Thereafter, only the container-like member 8 and the cover member 11 that are in direct contact with the sample may be discarded, and the mounting block 12a, the heating / cooling device 7 and the like may be used repeatedly.

  According to the chemical analyzer according to the first embodiment, the reaction vessel 5a is sealed with the cover member 11 to the solidified sample, so that the sample dispensed in the reaction vessel 5a does not evaporate, and The reaction vessel 5a can be sealed without leaving any gas.

(Second Embodiment)
As shown in FIG. 3, the chemical analyzer according to the second embodiment includes a mounting block 12b in which reaction tanks 5b and 5c for injecting the sample 10 are arranged, and a gas inlet / outlet hole 25. A sealing lid 21a that seals the surface of the reaction vessels 5b and 5c into which the sample 10 is injected, a sensor 24 that detects the state of the sample 10 provided in the sealing lid 21a, and the reaction vessel 5b that penetrates the sealing lid 21a, The injection needle 20 which injects the sample 10 into 5c is provided.

  The mounting block 12b is made of, for example, glass epoxy resin, fluorine resin such as polypropylene (PP) or polytetrafluoroethylene (PTFE), quartz, silicon, metal, or the like. Here, examples of the metal include nichrome, hastelloy, mnemonic, inconel, and stainless steel having low thermal conductivity. The mounting block 12b includes reaction vessels 5b and 5c. The sealing lid 21a seals the reaction tanks 5b and 5c, and includes an injection needle 20 and a gas inlet / outlet hole 25.

  As shown in FIG. 4, the injection needle 20 includes a plurality of connectors 27a, 27c for injecting the sample 10, and a plurality of valves 26a, 26b for conducting / blocking the flow of the sample 10 between the connectors 27a, 27c and the reaction tank. , 26c. Further, the flow path of the sample 10 from the first connector 27a to the first valve 26a, which is conductive / blocked by the first valve 26a, is from the second valve 26b, which is conductive / blocked by the first valve 28a and the second valve 26b. The flow path of the sample 10 following the reaction tank is the second flow path 28b, and the flow path of the sample 10 from the second connector 27c to the third valve 26c, which is conducted / blocked by the third valve 26c, is the third flow path 28c. .

  The first valve 26a, the second valve 26b, and the third valve 26c conduct / block the flow of the sample 10 inside the injection needle 20. As the structure of this valve, for example, a passive valve having a single beam structure may be provided inside the injection needle 20 to control the flow of the sample 10. Alternatively, the flow of the sample 10 may be controlled by changing the inner diameter of the injection needle 20 using a shape memory alloy or a piezoelectric element. Furthermore, you may use the solenoid valve which opens and closes with the force of an electromagnet (solenoid).

  The gas inlet / outlet holes 25 are closed when necessary, and the reaction vessels 5b and 5c are sealed. As the structure of the gas entrance / exit hole 25, for example, a shutter that is electrically or magnetically driven at an arbitrary timing may be used. Alternatively, the gas inlet / outlet holes 25 may be formed of a polymer absorber, and the gas inlet / outlet holes 25 may be blocked by the sample 10 soaking into the polymer absorber. Further, a passive stopper 29 may be used as shown in FIG. FIG. 5A is a cross-sectional view of the sealing lid 21a in which the gas inlet / outlet hole 25 is formed in a trapezoidal shape and the stopper 29 is disposed inside the gas inlet / outlet hole 25. FIG. When the sample 10 is filled in the reaction vessel and reaches the height of the sealing lid 21a, the stopper 29 is pushed up by the sample 10. The reaction vessel can be sealed by the stopper 29 being in close contact with the inner wall of the gas inlet / outlet hole 25. In this case, the material of the plug 29 may be any material having a specific gravity smaller than that of the sample 10. FIG. 5 (b) is a view of the stopper 29 as seen from the reaction tank side. A cross-shaped stopper is hermetically sealed at the lower part of the gas inlet / outlet hole 25 so that the stopper 29 does not fall into the reaction tank. It is provided in a form following the lid 21a. Of course, the stopper is not limited to a cross shape as long as the stopper 29 does not drop into the reaction vessel.

  The sensor 24 measures conditions such as the height, temperature, and pH value of the samples inside the reaction vessels 5b and 5c. In FIG. 3, the sensor 24 is installed in the upper part of the sealing lid 21a. However, the sensor 24 may be installed in the gas entry / exit hole 25 in the sealing lid 21a. In order to automatically detect whether or not the sample 10 in the reaction vessels 5b and 5c has reached the height of the sealing lid 21a, an electrode is placed on the sealing lid 21a and the electrical resistance value between the electrodes is monitored. That's fine. At the moment when the sample 10 reaches the height of the sealing lid 21a, the electric resistance value decreases. Further, in order to measure the temperature of the sample 10 inside the reaction vessels 5b and 5c, a thermocouple, a resistance temperature detector, or the like may be used. The PH value may be measured using a glass electrode method.

  According to the chemical analyzer according to the second embodiment, the sample dispensed in the reaction vessels 5b and 5c does not evaporate, and the reaction vessels 5b and 5c can be sealed without leaving any gas. Further, the sample 10 after analysis can be easily extracted.

  Next, a method for performing dispensing using the chemical analyzer according to the second embodiment will be described with reference to FIG. In the following description, there is a place where the chemical analyzer shown in FIG. 3 is described as a specific example, but all of the injection needles 20 shown in FIG. 3 have the structure shown in detail in FIG. To do.

  (A) First, in step S101, the valve is opened. At this time, like the reaction tank Ab on the left side of FIG. 3, when the first valve 26a and the second valve 26b are opened and the third valve 26c is closed, the flow path of the sample 10 connected from the first connector 27a to the reaction tank 5b. Is formed. When the first valve 26a is closed and the second valve 26b and the third valve 26c are opened as in the reaction tank 5c on the right side, a flow path for the sample 10 connected from the second connector 28c to the reaction tank 5c is formed. Further, the gas inlet / outlet holes 25 are left open. Thereby, when the sample 10 is poured into the reaction vessels 5b and 5c, the gas inside the reaction vessels 5b and 5c can escape to the outside of the reaction vessels 5b and 5c through the gas inlet / outlet holes 25.

  (B) Next, in step S102, a sample to be dispensed is supplied to the connector. For example, in the reaction tank 5b on the left side of FIG. 3, the sample 10 is supplied to the first connector 27a. In this way, one type of sample may be supplied, or all of the first valve 26a, the second valve 26b, and the third valve 26c shown in FIG. 4 are opened, and both the first connector 27a and the second connector 27c are connected. Samples may be supplied and a plurality of types of samples 10 may be supplied by combining channels with multiple inputs and one output.

  In FIG. 6, it has been described that the sample is supplied to the connector after the valve and the gas inlet / outlet hole 25 are opened. However, after the sample is supplied to the connector, the valve and the gas inlet / outlet hole 25 are opened. I do not care.

  (C) Next, in step S103, the sample is supplied to the reaction vessel. For example, in the reaction tank 5b on the left side of FIG. 3, the sample 10 is supplied from the first connector 27a to the reaction tank 5b. At this time, the state of the sample 10 in the reaction vessel 5b is constantly monitored by the sensor 24 installed on the sealing lid 21a.

  (D) In step S104, the sensor 24 detects whether the sample 10 has reached the height of the sealing lid 21a. When it detects, it progresses to step S105 and makes the hole 25 for gas in / out closed. In FIG. 3, at least the second valve 26b is closed, and the flow path of the sample 10 is shut off. When not detecting, it returns to step S103 and continues supplying a sample to a reaction tank.

  (E) Next, in step S106, the sample 10 is analyzed. For example, when nucleic acid amplification is performed on the assumption that the sample 10 is a nucleic acid (DNA), the sample 10 is heated, the DNA is dissociated at about 95 ° C., annealed at about 55 ° C., and replicated at about 70 ° C. Amplify.

  (F) After the analysis is completed, the valve is opened in step S107. If necessary, the gas entry / exit holes 25 are also opened. For example, in the reaction tank 5b on the left side of FIG. 3, the first valve 26a and the second valve 26b are opened.

  (G) Next, in step S108, the sample 10 is extracted to the connector. For example, in the reaction tank 5b on the left side of FIG. 3, the sample 10 is extracted to the first connector 27a. The connector from which the sample 10 is extracted may not be the connector that supplied the sample. For example, the sample 10 in the reaction tank 5b on the left side of FIG. 3 may be supplied from the first connector 27a and extracted to the second connector 27c. In this case, the second valve 26b and the third valve 26c are opened.

Here, in the dispensing method according to the second embodiment, a force for feeding the sample 10 inside the injection needle 20 into the reaction vessels 5b and 5c will be described. Considering the injection needle 20 that can be dispensed into the reaction vessels 5b and 5c, for example, the injection needle 20 having an outer diameter of 0.2 mm and an inner diameter of 0.1 mm, the surface tension on the inner side surface of the injection needle 20 rather than the gravity applied to the sample 10 Therefore, the sample 10 does not flow down the inside of the injection needle 20 only by supplying the sample 10 to the connector. Therefore, it is necessary to apply a power output to the sample 10 inside the injection needle 20. As this method, for example, the sample inside the injection needle 20 may be directly sent out with a rod having a diameter slightly smaller than the inner diameter of the injection needle 20. Further, a pump (not shown), a tube (not shown), or the like may be connected to the upper portion of the connector, and a positive pressure may be applied to the connector to generate a sample feeding output. Further, when the gas inlet / outlet hole 25 is in an open state, a pump, a tube, or the like is connected to the upper part of the gas inlet / outlet hole 25 to apply a negative pressure to the gas inlet / outlet hole 25, thereby generating a sample output. May be. Alternatively, the solution in the injection needle 20 may be sent out by the peristaltic movement of the injection needle 20.

  Conversely, when the sample present in the reaction vessels 5b and 5c is extracted to the first connector 27a, the first valve 26a and the second valve 26b are opened and the third valve 26c is closed. A pump, a tube or the like is connected to the upper part of the first connector 27a, and a negative pressure is applied to the first connector 27a, thereby generating a sample output. Alternatively, when the gas entry / exit hole 25 is in an open state, a pump, a tube, or the like is connected to the upper part of the gas entry / exit hole 25 and positive pressure is applied to the gas entry / exit hole 25 to generate a sample output. May be. Further, the sample inside the injection needle 20 may be sent out by the peristaltic movement of the injection needle 20.

  In the chemical analyzer according to the second embodiment, the first flow path 28a has a structure branched to the second flow path 28b and the third flow path 28c, but the third flow path 28c is omitted. Of course, the structure may not be branched, or the number of branches of the flow path may be increased to have a structure having a plurality of flow paths.

  In the chemical analyzer according to the second embodiment, the injection needle 20 is described as being fixed to the sealing lid 21a. However, the injection needle 20 can be removed and sealed before the sample 10 is injected. You may insert in the lid | cover 21a. In this case, the injection needle 20 is removed after the analysis of the sample 10 is completed and the sample 10 is extracted. By making the injection needle 20 removable, the replacement and cleaning of the injection needle 20 can be facilitated.

  According to the dispensing method according to the second embodiment, the sample dispensed in the reaction vessels 5b and 5c does not evaporate, and the reaction vessels 5b and 5c can be sealed without leaving any gas. Further, the sample 10 after analysis can be easily extracted.

(Third embodiment)
As shown in FIGS. 7 and 8, the chemical analyzer according to the third embodiment is for mounting having a plurality of reaction vessels 5d for analyzing a sample and a well 31 in which the plurality of reaction vessels 5d are arranged. A block 12c and a plurality of sealing lids 21b for sealing the surface into which the sample 10 is injected into each of the plurality of reaction vessels 5d are provided. The mounting block 12c is made of, for example, glass epoxy resin, fluorine resin such as polypropylene (PP) or polytetrafluoroethylene (PTFE), quartz, silicon, metal, or the like. Here, examples of the metal include nichrome, hastelloy, mnemonic, inconel, and stainless steel having low thermal conductivity. The sealing lid 21b is a lid that seals the reaction tank 5d containing the sample so as to prevent air from entering.

  FIG. 9 is a cross-sectional view showing details of the structure of the reaction vessel 5d and the sealing lid 21b. The chemical analyzer according to the third embodiment includes a container-shaped member 8 sandwiched between a first bonding member 38 and a second bonding member 37, and a reaction for injecting a sample 10. The tank 5d, the mounting block 12c having a well for arranging the reaction tank 5d, the third bonding member 36 in contact with the second bonding member 37, and the third bonding member 36 are opposed to each other. The fourth bonding member 35 includes a sealing lid 21b that seals a surface of the reaction tank 5d that includes the cover member 11 that is sandwiched around the surface and into which the sample 10 is injected. The 3rd member 36 for adhesion takes the corner inside reaction tank 5d, and makes it the shape which cannot collect air. The container-like member 8 and the cover member 11 are made of a material such as a flexible resin that is resistant to a chemical reaction such as polypropylene having a thickness of about 10 to 50 μm, like the chemical analysis apparatus according to the first embodiment. Made from. The container-like member 8 and the cover member 11 are materials that are relatively difficult to bond. In order to bond these, chemical or physical treatment for obtaining a surface suitable for bonding such as corona treatment, acid treatment, sand blast treatment, and primer treatment must be performed. Therefore, the container-like member 8 and the cover member 11 are bonded together by bonding the bonding members 35, 36, 37, 38 sandwiching the periphery of the container-shaped member 8 and the cover member 11. The material of the bonding members 35, 36, 37, and 38 is metal, glass, resin other than Teflon (registered trademark) / polypropylene, etc., which are relatively easy to bond. Further, a metal or resin thin film formed on the surface of an arbitrary member may be used as the bonding members 35, 36, 37, and 38. As a method for forming the thin film, an appropriate method may be used according to the base material such as sputtering, vapor deposition, or dipping.

  In FIG. 9, the third bonding member 36 and the second bonding member 37 are coupled with an adhesive 39, whereby the inside of the reaction vessel 5d is sealed with a sealing lid 21b. When the sealing lid 21b is fitted in the reaction vessel 5d, the lower surface of the cover member 11 and the sample in the reaction vessel 5d are brought into close contact with each other by surface tension, and air inside the reaction vessel 5d can be excluded. When the sample 10 in the reaction vessel 5d is small, the cover member 11 having flexibility is lowered downward so that air can be excluded. When the sample 10 is large, the excess sample 10 is removed from the reaction vessel 5d. The air can be eliminated. Further, instead of the adhesive 39, the bonding surfaces of the third bonding member 36 and the second bonding member 37 are heated by a heater, and the third bonding member 36 and the second bonding member 37 are moved. The reaction tank 5d may be sealed with the sealing lid 21b by welding and bonding. Further, as shown in FIG. 10, when the sealing lid 21b is fitted into the reaction vessel 5d, the third bonding member 36 is provided with a convex portion and the second bonding member 37 is provided with a concave portion, and the reaction is performed so that these are fitted. The tank 5d may be sealed.

  In addition, as shown in FIG. 11, each of the plurality of reaction vessels 5d includes a blocking member 40, and when the sealing lid 21b is fitted to the reaction vessel 5d, the extra sample 10 removed outside the reaction vessel 5d is removed. You may make it receive. The blocking member 40 also functions as a partition of the sample 10 from the adjacent reaction tank 5d.

  According to the chemical analyzer according to the third embodiment, the sample dispensed in the reaction vessel 5d does not evaporate, and the reaction vessel 5d can be sealed without leaving any gas. Further, even the reaction tank 5d and the sealing lid 21b that are difficult to bond can be easily bonded by the bonding members 35, 36, 37, and 38.

  Next, a method for dispensing using the chemical analyzer according to the third embodiment will be described with reference to FIG.

  (A) First, in step S201, the sample 10 is dispensed into the reaction vessel 5d by a dispensing device. This dispensing apparatus may be the same as the dispensing apparatus described in the dispensing method according to the first embodiment.

  (B) Next, in step S202, the sealing lid 21b is fitted into the reaction vessel 5d. Then, the third bonding member 36 that sandwiches the periphery of the lower portion of the cover member 11 and the second adhesive member 37 that sandwiches the periphery of the upper portion of the container-like member 8 are combined. As this bonding method, the third bonding member 36 and the second bonding member 37 are bonded using an adhesive 39. Alternatively, the third adhesive member 36 may be provided with a convex portion and the second adhesive member 37 may be provided with a concave portion, and these may be coupled so as to fit with each other. Thereby, the reaction vessel 5d and the sealing lid 21b are sealed.

  (C) Next, in step S203, the reaction vessel 5d sealed with the sealing lid 21b is placed in the well 31 of the mounting block 12c.

  (D) Next, in step S204, the sample 10 is analyzed. For example, when nucleic acid amplification is performed on the assumption that the sample 10 is a nucleic acid (DNA), the sample 10 is heated, the DNA is dissociated at about 95 ° C., annealed at about 55 ° C., and replicated at about 70 ° C. Amplify.

  (E) After the analysis is completed, the container-like member 8 containing the sample 10 is removed from the mounting block 12c. Thereafter, only the container-like member 8 and the cover member 11 that are in direct contact with the sample 10 may be discarded, and the mounting block 12c and the like may be used repeatedly.

  In the above dispensing method, the sample 10 is dispensed into the reaction tank 5d and then placed on the mounting block 12c. However, even if the sample 10 is dispensed after the reaction tank 5d is placed on the placing block 12c. I do not care.

  According to the dispensing method according to the third embodiment, the sample dispensed in the reaction vessel 5d does not evaporate, and the reaction vessel 5d can be sealed without leaving any gas. Further, even the reaction tank 5d and the sealing lid 21b that are difficult to bond can be easily bonded by the bonding members 35, 36, 37, and 38.

(Other embodiments)
Although the present invention has been described according to the above-described embodiments, it should not be understood that the descriptions and drawings constituting a part of this disclosure limit the present invention. From this disclosure, various alternative embodiments, examples, and operational techniques will be apparent to those skilled in the art.

  For example, in the first embodiment of the present invention, the mounting block 12a includes the heating / cooling device 7, but this apparatus may be applied to the second and third embodiments. That is, in the second and third embodiments, the mounting blocks 12b and 12c may be provided with a plurality of heating / cooling devices, and the temperature may be controlled for each of the reaction vessels 5b, 5c, and 5d.

  Further, the dispensing method according to the first embodiment may be applied to the dispensing method according to the third embodiment of the present invention. That is, in the third embodiment, the mounting block 12c is provided with the heating / cooling device 7, and the sample 10 is dispensed while solidifying and sealed with the sealing lid 21b, and then the sample 10 is melted. I do not care. Further, the blocking member 40 described in the third embodiment may be used in the chemical analyzers according to the first and second embodiments. Thus, it goes without saying that the chemical analyzers and dispensing methods according to the first to third embodiments may be used in combination.

  As described above, the present invention naturally includes various embodiments not described herein. Therefore, the technical scope of the present invention is defined only by the invention specifying matters according to the scope of claims reasonable from the above description.

(A) is sectional drawing of the chemical analyzer which concerns on 1st Embodiment. (B) is the figure which looked at the chemical analyzer which concerns on 1st Embodiment from the top. It is the method of dispensing a sample to the chemical analyzer which concerns on 1st Embodiment. It is sectional drawing of the chemical analyzer which concerns on 2nd Embodiment. It is sectional drawing of the injection needle of the chemical analyzer which concerns on 2nd Embodiment. (A) is sectional drawing of the sealing lid of the chemical analyzer which concerns on 2nd Embodiment. (B) is the figure which looked at the sealing lid provided with the stopper from the reaction tank side. It is a flowchart of the dispensing method which concerns on 2nd Embodiment. It is a perspective view of the chemical analyzer which concerns on 3rd Embodiment. It is sectional drawing of the chemical analyzer which concerns on 3rd Embodiment. It is a detailed sectional view of a chemical analysis device concerning a 3rd embodiment. It is another detailed sectional view of the chemical analysis device concerning a 3rd embodiment. It is the perspective view which mounted | wore with the member for interruption | blocking to the chemical analyzer which concerns on 3rd Embodiment. It is a flowchart of the dispensing method which concerns on 3rd Embodiment. It is a perspective view of the conventional μ-TAS.

Explanation of symbols

5a, 5b, 5c, 5d Reaction tank 6 Dispensing needle 7 Heating / cooling device 8 Container-like member 9 Dispensing device 10 Sample 10a Solid sample 10b Liquid sample 11 Cover member 12a, 12b, 12c Mounting block 20 Injection needle 21a, 21b Sealing lid 24 Sensor 25 Gas inlet / outlet 26a First valve 26b Second valve 26c Third valve 27 Connector 27a First connector 27c Second connector 28a First flow path 28b Second flow path 28c Third flow path 29 Plug 31 Well 35 Fourth bonding member 36 Third bonding member 37 Second bonding member 38 First bonding member 39 Adhesive 40 Blocking member

Claims (6)

A reaction vessel for injecting a sample, comprising a container-like member sandwiched between the first and second adhesive members,
A mounting block having a well for disposing the reaction vessel;
The sample of the reaction vessel comprising a cover member sandwiched between a third adhesive member in contact with the second adhesive member and a fourth adhesive member facing the third adhesive member. A chemical analysis device comprising: a sealing lid that seals a surface into which the gas is injected. The chemical analysis apparatus according to claim 1, wherein the second bonding member and the third bonding member are bonded with an adhesive. The said 2nd member for adhesion and the said 3rd member for adhesion are respectively provided with the recessed part and the convex part, and are couple | bonded by fitting the said recessed part and the said convex part. Chemical analysis equipment. A step of dispensing a sample into a reaction vessel for injecting the sample, comprising a container-like member sandwiched between the first bonding member and the second bonding member; and
Sealing comprising a cover member sandwiched between a third bonding member in contact with the second bonding member and a fourth bonding member facing the third bonding member in the reaction vessel. Fitting the lid;
Disposing the reaction vessel on the mounting block as described above. 5. The dispensing method according to claim 4, wherein the fitting step includes a step of joining the second adhesive member and the third adhesive member with an adhesive. 5. The fitting step according to claim 4, wherein the fitting step includes a step of fitting by fitting a concave portion and a convex portion respectively provided in the second bonding member and the third bonding member. Dispensing method.

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