WO2020179053A1 - Liquid-feeding cartridge for temperature-controlling apparatuses - Google Patents

Liquid-feeding cartridge for temperature-controlling apparatuses Download PDF

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Publication number
WO2020179053A1
WO2020179053A1 PCT/JP2019/009059 JP2019009059W WO2020179053A1 WO 2020179053 A1 WO2020179053 A1 WO 2020179053A1 JP 2019009059 W JP2019009059 W JP 2019009059W WO 2020179053 A1 WO2020179053 A1 WO 2020179053A1
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Prior art keywords
layer
liquid
temperature control
feeding
control device
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PCT/JP2019/009059
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French (fr)
Japanese (ja)
Inventor
航 佐藤
長岡　嘉浩
周平 山本
太朗 中澤
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株式会社日立ハイテク
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Priority to JP2021503367A priority Critical patent/JP7150138B2/en
Priority to PCT/JP2019/009059 priority patent/WO2020179053A1/en
Publication of WO2020179053A1 publication Critical patent/WO2020179053A1/en

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    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12M—APPARATUS FOR ENZYMOLOGY OR MICROBIOLOGY; APPARATUS FOR CULTURING MICROORGANISMS FOR PRODUCING BIOMASS, FOR GROWING CELLS OR FOR OBTAINING FERMENTATION OR METABOLIC PRODUCTS, i.e. BIOREACTORS OR FERMENTERS
    • C12M1/00—Apparatus for enzymology or microbiology
    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N35/00—Automatic analysis not limited to methods or materials provided for in any single one of groups G01N1/00 - G01N33/00; Handling materials therefor
    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N37/00—Details not covered by any other group of this subclass

Definitions

  • the present invention relates to a liquid feeding cartridge for a temperature control device.
  • a sample solution containing DNA and a solution containing a reagent for amplifying DNA are mixed, denatured into a single strand at 94°C, and a complementary strand is synthesized at 60°C.
  • DNA can be amplified exponentially.
  • the temperature rises or falls excessively with respect to the temperature required by the reagent a problem that the target DNA is not amplified occurs, so that highly accurate temperature control is required.
  • the development of a flow path chip that realizes liquid transfer on a disposable substrate is underway, and the elasticity provided on the surface of the flow path chip. It has been reported that a chip is delivered by utilizing deformation of a membrane. Further, in order to realize the PCR method on the liquid feeding chip after the liquid is fed, the development of a structure for giving a temperature change using a Peltier element is underway.
  • Patent Document 1 while applying pressure to the inside of the container unit that stores the liquid sample. , A method of heating a liquid sample is disclosed. Further, Patent Document 2 describes a configuration including an upper hard substrate, a membrane layer, a pedestal substrate, and at least one support cup substrate having a recess having an opening formed therein.
  • Patent Document 1 by applying pressure to the solution sealed with the membrane and the substrate, the solution is pressed against the temperature control block through the membrane, and the heat exchange efficiency with the temperature control block is improved.
  • the temperature control structure described in Patent Document 1 requires a mechanism for applying pressure to the reaction container portion that controls the temperature of the solution, which complicates the liquid feeding mechanism.
  • the membrane undergoes thermal deformation with temperature change. Occurs, and the contact thermal resistance changes due to this thermal deformation, so there is a problem that it is difficult to give a uniform and highly accurate temperature change.
  • Patent Document 2 the membrane undergoes thermal deformation with a temperature change, and the contact thermal resistance changes with the thermal deformation, so that it is difficult to give a uniform and highly accurate temperature change.
  • the present invention provides a high-speed and highly accurate liquid-feeding cartridge for a temperature control device, which suppresses deterioration of contact thermal resistance due to thermal deformation.
  • the liquid feeding cartridge for a temperature control device is a liquid feeding cartridge that forms a flow path in a gap between a second layer that can be arranged in a temperature adjusting unit and the second layer.
  • the liquid transfer chip is arranged on the upper side of the second layer or on the lower side of the second layer, and is made of an elastic body.
  • another liquid feeding cartridge for a temperature control device includes a liquid feeding tip that forms a flow path in a gap between a second layer that can be arranged in the temperature control unit and the second layer.
  • a first layer which is disposed on the lower side of the second layer, which is the side opposite to the liquid delivery chip, and which is made of an elastic body and has a linear expansion coefficient larger than that of the second layer. It is characterized by.
  • FIG. 3 is a schematic top view of a temperature control device according to a first embodiment of the present invention.
  • 3 is a schematic side view of the temperature control device according to the first embodiment.
  • FIG. It is a block diagram of the liquid feeding cartridge shown in FIG. 1 and FIG.
  • FIG. 2 is a cross-sectional view taken along the line A-A′ for explaining the structure of the temperature control device in FIG. 1.
  • FIG. 2 is a B-B′ cross-sectional view illustrating the structure of the temperature control device in FIG. 1.
  • FIG. 3 is a diagram showing a solution introduction state of a liquid-feeding cartridge according to Example 1.
  • FIG. 3 is a diagram showing a flow path hermetically sealed state of a liquid delivery cartridge according to the first embodiment.
  • FIG. 3 is a diagram showing a state in which a solution of a liquid-fed cartridge according to Example 1 is held in a temperature control channel.
  • FIG. 6 is a diagram showing a movement state of a solution of a liquid-fed cartridge according to Example 1 from a temperature control channel.
  • FIG. 3 is a diagram showing a solution discharge state of a liquid-feeding cartridge according to the first embodiment. It is sectional drawing explaining the structure of the temperature control apparatus by Example 2 which concerns on the other Example of this invention. It is a figure which shows the modification of FIG. It is sectional drawing explaining the structure of the temperature control apparatus by Example 3 which concerns on the other Example of this invention. It is sectional drawing explaining the structure of the temperature control apparatus by Example 4 which concerns on the other Example of this invention. It is sectional drawing explaining the structure of the temperature control apparatus by Example 5 which concerns on the other Example of this invention.
  • the “chemical analysis device” to which the liquid delivery cartridge of the present invention is applied includes a DNA analysis device, a nucleic acid amplification device, and a gene test device. Embodiments of the present invention will be described below with reference to the drawings.
  • FIG. 1 is a schematic top view of the temperature control device 20 according to the first embodiment according to the first embodiment of the present invention.
  • FIG. 2 is a schematic side view of the temperature control device 20.
  • the shape of the flow path formed by the liquid feed cartridge 1 and the liquid feed control unit 5 is shown by a broken line.
  • the temperature control device 20 includes a liquid feed cartridge 1, a liquid feed control unit 5, and a temperature control unit 16.
  • FIG. 3 shows the structure of each layer constituting the liquid feeding cartridge 1.
  • the liquid feed cartridge 1 is composed of a first layer 4 made of a liquid feed tip 2 and an elastic body, and a second layer 3 made of a material having a coefficient of linear expansion smaller than that of the first layer, and is composed of a liquid feed control unit 5.
  • the liquid feed cartridge 1 is removable from the upper surface of the liquid feed control unit 5.
  • the liquid-feeding chip 2 has an introduction hole 10 for introducing a solution and a discharge hole 11 for discharging the solution.
  • a groove is formed on the bottom surface of the liquid feeding tip 2 to form a flow path 8 and a temperature control flow path 8a.
  • the introduction hole 10 and the discharge hole 11 communicate with each other from the upper surface to the lower surface of the liquid feeding chip 2, and the solution can be moved through the channel 8 and the temperature control channel 8a.
  • the second layer 3 has an opening 3a having substantially the same shape as the first liquid feeding valve 9a, the second liquid feeding valve 9b, and the third liquid feeding valve 9c formed in the liquid feeding control unit 5.
  • the first layer 4 has an opening 4a having substantially the same shape as the temperature control flow path 8a.
  • the liquid feed control unit 5 is formed with an opening 9d for fixing the temperature control unit 16 and recesses serving as a first liquid feed valve 9a, a second liquid feed valve 9b, and a third liquid feed valve 9c. ..
  • through holes 12 are formed in the bottom surfaces of the first liquid feeding valve 9a, the second liquid feeding valve 9b, and the third liquid feeding valve 9c. Further, the through hole 12 is connected to a device (not shown) that controls the introduction and discharge of a fluid such as air.
  • FIG. 4 shows a cross-sectional view of the temperature control device 20 shown in FIG. 1 in the AA'direction.
  • the liquid feed control unit 5 and the temperature control unit 16 are fixed to the bottom surface of the liquid feed cartridge 1.
  • the temperature control block 6 constituting the temperature control unit 16 contacts the second layer 3 through the opening 4a (FIG. 3) formed in the first layer 4, and the temperature control of the liquid feeding tip 2 is performed. It is fixed to the bottom surface of the channel 8a.
  • the first layer 4 formed in the liquid feed control unit 5 does not come into contact with the temperature control block 6.
  • the second layer 3 has an opening 3a substantially the same as the first liquid feeding valve 9a, the second liquid feeding valve 9b, and the third liquid feeding valve 9c, and the opening 3a and the liquid feeding valve Attach so that the positions of are the same. Therefore, the second layer 3 is not formed on the upper part of the opening of the liquid feed valve.
  • the second layer 3 is disposed on the bottom surface of the temperature control channel 8a formed in the liquid feeding chip 2, and the temperature is controlled by being pressed by the temperature control block 6 through the opening 4a formed in the first layer 4.
  • the bottom surface of the flow control channel 8a is sealed.
  • the solution 13 is placed in the introduction hole 10 of the liquid feeding chip 2 (solution introduction state).
  • air is introduced into the second liquid feeding valve 9b through the through hole 12 to push up the first layer 4, that is, to push up the second liquid feeding valve 9b,
  • the channel 8 is sealed by bringing the layer 4 of No. 1 into contact with the bottom surface of the liquid-feeding chip 2 (channel closed state).
  • the first layer 4 is deformed, that is, by pulling down the first liquid feed valve 9a, the solution 13 arranged in the introduction hole 10 flows through the flow path.
  • the liquid is sucked through the first liquid feeding valve 9 a through the valve 8. Further, as shown in FIG. 6C, first the third liquid feed valve 9c is pushed up to seal the flow path 8, and then the second liquid feed valve 9b is pulled down to transfer the solution 13 to the temperature control flow path 8a in the liquid feed tip 2. To the solution by pushing up the first liquid feed valve 9a to seal the flow passage 8, lowering the third liquid feed valve 9c to open the flow passage 8, and pushing up the second liquid feed valve 9b. 13 is held in the temperature control flow path 8a (a state in which the solution is held in the temperature control flow path).
  • the temperature of the temperature control block 6 can be changed by the temperature control element 7 that constitutes the temperature control unit 16, and the temperature of the solution 13 can be changed via the second layer 3.
  • the third liquid feed valve 9c is pushed up to seal the flow path 8, and the first liquid feed valve 9a and the third liquid feed valve 9c are pulled down. Then, the solution 13 advances to the area of the second liquid feeding valve 9b (movement state of the solution from the temperature control channel). Further, as shown in FIG. 6E, the third liquid feed valve 9c is pulled down to open the flow path 8, and the first liquid feed valve 9a and the second liquid feed valve 9b are pushed up to discharge the solution 13 into the discharge hole 11.
  • the solution 13 that has been subjected to the temperature treatment can be taken out from the liquid feeding cartridge 1 (solution discharge state).
  • the temperature control element 7 by installing a temperature sensor (not shown) required for controlling the temperature by the temperature control element 7 in the temperature control block 6, it is possible to confirm that the temperature change is a desired one. For example, a sample containing DNA and a reagent containing an enzyme that amplifies DNA are mixed, and the liquid is sent to the temperature control flow path 8a on the liquid feed cartridge 1, and the temperature is repeatedly changed to 94 ° C and 60 ° C. By so doing, the DNA can be amplified and analyzed.
  • the thermal deformation of the bottom surface forming the temperature control flow path 8a is small, and the contact thermal resistance between the temperature control block 6 and the second layer 3 is kept uniform. Therefore, the temperature change by the temperature adjustment unit 16 can be accurately transmitted to the solution 13.
  • the temperature control block 6 since the temperature control block 6 is in contact with only the second layer 3 having a small thermal deformation and not in contact with the first layer 4 having a large thermal deformation, the heat accompanying the temperature change is generated. Since the deformation is suppressed, a uniform contact state is maintained and the contact thermal resistance does not change.
  • the flow path 8 is not limited to one system, and an introduction hole and a flow path for sending and mixing a plurality of solutions.
  • a liquid-feeding chip having a plurality of discharge holes may be used.
  • the temperature control block 6 is intended to efficiently transfer the temperature change of the temperature control element 7 to the solution 13 held in the temperature control channel 8a, it is preferably a metal material having high thermal conductivity. It is desirable to form it with aluminum or copper, for example.
  • the temperature control element 7 may have a structure in which the temperature is adjusted by passing a Peltier element or heating using a heater or a cooling medium.
  • the liquid transfer control unit 5 has a structure in which the first layer 4 is deformed by using air, the first layer 4 may be deformed by using water or oil.
  • the second layer 3 is preferably made of a material having a small linear expansion coefficient, and is preferably made of polyimide, polyester, Teflon (registered trademark) or the like.
  • FIG. 7 is a sectional view for explaining the structure of a temperature control device according to a second embodiment of the present invention
  • FIG. 8 is a view showing a modification of FIG.
  • This example differs from Example 1 in that the second layer 3 has an adhesive layer 14.
  • Other configurations are the same as those in the above-described first embodiment, and in the following, the same components as those in the first embodiment will be denoted by the same reference numerals and overlapping description of the first embodiment will be omitted.
  • the adhesive layer 14 is formed on both surfaces of the second layer 3.
  • the adhesive layer 14 is a flow path 8 formed in the liquid feed chip 2, a first liquid feed valve 9a, a second liquid feed valve 9b, and a third liquid feed valve 9c formed in the liquid feed control unit 5.
  • the second layer 3 is adhered to the liquid-feeding chip 2 and the first layer 4 via the adhesive layer 14, and the gap between the second layer 3 and the liquid-feeding chip 2 and the first layer are provided. The leakage of the liquid and the leakage of the vapor from the gap between the layer 4 and the second layer 3 are suppressed.
  • the contact state of the second layer 3 with the temperature control block 6 does not change, and the temperature control state is stable.
  • the portion of the adhesive layer 14 that is in contact with the temperature control block 6 is removed (as shown in FIG. 8) and the second layer 3 and the temperature control block 6 are directly contacted. You may.
  • the gap between the second layer 3 and the liquid delivery chip 2 and the gap between the first layer 4 and the second layer 3 are provided by the adhesive layer 14. Leakage of liquid and steam is suppressed. Further, since the second layer 3 is adhered to the temperature control block 6, the contact state of the second layer 3 with the temperature control block 6 does not change, and the temperature control state becomes stable.
  • FIG. 9 is a sectional view illustrating the structure of a temperature control device according to a third embodiment of the present invention.
  • the present embodiment is different from the first embodiment in that the convex portion 15 is provided around the temperature control channel 8a in the liquid feeding chip 2.
  • Other configurations are the same as those in the first embodiment, and the same components as those in the first embodiment are designated by the same reference numerals, and the description overlapping with the first embodiment will be omitted.
  • the flow channel 8 is formed by the concave portion formed in the liquid feeding chip 2, and the convex portion 15 is provided around the temperature control flow channel 8a.
  • the pressure that presses the second layer 3 only around the temperature control flow path 8a increases, and it is possible to suppress the leakage of liquid and the leakage of vapor from the temperature control flow path 8a.
  • the convex portion 15 formed around the temperature control flow path 8a is not limited to a single step, and for example, a concave portion is formed in the temperature control block 6 and a comb tooth shape is formed to further press the pressing surface. The pressure may be increased.
  • FIG. 10 is a sectional view illustrating the structure of a temperature control device according to a fourth embodiment of the present invention.
  • This embodiment is different from the first embodiment in that the liquid feeding chip 2 and the first layer 4 are brought into close contact with each other and the second layer 3 is constructed on the lower surface of the first layer 4.
  • Other configurations are the same as those in the first embodiment, and the same components as those in the first embodiment are designated by the same reference numerals, and the description overlapping with the first embodiment will be omitted.
  • the first layer 4 is brought into close contact with the liquid feeding cartridge 1 and the second layer 3 is brought into close contact with the lower surface thereof. That is, as compared with the above-described first embodiment, the flow path 8 is NC (normally closed) in this embodiment. Therefore, since the liquid-feeding chip 2 and the first layer 4 made of an elastic body can be brought into close contact with each other, it is possible to prevent liquid leakage and vapor leakage from the temperature control channel 8a.
  • the second layer 3 may have an adhesive layer, and by applying a heat conductive sheet or heat conductive grease to the interface between the temperature control block 6 and the temperature control channel 8a, the contact thermal resistance of the interface is reduced. It may be a structure.
  • FIG. 11 is a sectional view for explaining the structure of a temperature control device according to a fifth embodiment of the present invention.
  • the first layer 4 is brought into close contact not only with the liquid delivery control unit 5 but also with the temperature control block 6, and further the second layer 3 is brought into close contact with the first layer 4 in the region of the temperature control block 6.
  • the point that the temperature control flow path 8a is constructed between the liquid sending chip 2 and the first embodiment is different.
  • Other configurations are the same as those in the first embodiment, and the same components as those in the first embodiment are designated by the same reference numerals, and the description overlapping with the first embodiment will be omitted.
  • the first layer 4 is brought into close contact not only with the liquid delivery control unit 5 but also with the temperature control block 6, and the second layer 3 is further applied in the region of the temperature control block 6.
  • the structure is such that it is in close contact with. That is, as compared with the above-described first embodiment, in the present embodiment, the first layer 4 is not provided with the opening 4a (FIG. 3) having substantially the same shape as the temperature control channel 8a, and the first layer 4 is not provided. There is no opening. Therefore, it is possible to prevent liquid leakage or vapor leakage from the temperature control flow path 8a to the outside.
  • the second layer 3 and the liquid delivery chip 2 are in close contact with each other in the vicinity of the temperature control flow path 8a, so that liquid leakage or vapor is generated. Can be prevented from leaking.
  • the present invention is not limited to the above-described embodiments, but includes various modifications.
  • the above-described embodiments have been described in detail in order to explain the present invention in an easy-to-understand manner, and are not necessarily limited to those having all the configurations described.
  • a part of the configuration of one embodiment can be replaced with the configuration of another embodiment, and the configuration of another embodiment can be added to the configuration of one embodiment.

Abstract

Provided is a high-speed and highly accurate liquid-feeding cartridge that is for temperature controlling apparatuses and that suppresses deterioration of contact thermal resistance resulting from thermal deformation. This liquid-feeding cartridge 1 for temperature control apparatuses is provided with: a second layer 3 that can be provided to a temperature adjustment part 16; a liquid-feeding chip 2 that forms a flow path in a gap from the second layer 3; and a first layer 4 that has a higher linear expansion coefficient than the second layer 3, that is formed of an elastic body, and that is disposed, outside an area of the temperature adjustment part 16, on the lower side of the second layer 3 or on the upper side of the second layer 3 on which side the liquid-feeding chip 2 is located.

Description

温度制御装置用送液カートリッジLiquid transfer cartridge for temperature control device
　本発明は、温度制御装置用送液カートリッジに関する。 The present invention relates to a liquid feeding cartridge for a temperature control device.
　近年、遺伝子検査は研究用途のみならず、オーダーメイド医療や個人を識別する鑑定など広い用途で利用されるようになり、精度だけでなく検査時間の短縮が望まれている。遺伝子検査を実施する場合、ＤＮＡ（Ｄｅｏｘｙｒｉｂｏｎｕｃｌｅｉｃ　ａｃｉｄ、デオキシリボ核酸）を含む試料を取得したのち、試料中の微量のＤＮＡを増幅させてから分析を行うことで高精度な分析を実現している。ここでＤＮＡを増幅させる方法として、ＰＣＲ（Ｐｏｌｙｍｅｒａｓｅ　Ｃｈａｉｎ　Ｒｅａｃｔｉｏｎ、ポリメラーゼ連鎖反応）法が広く利用されている。ＰＣＲ法では、ＤＮＡを含む試料溶液とＤＮＡを増幅させる試薬を含む溶液を混合し、たとえば９４°Ｃで１本鎖に変性させ、６０°Ｃで相補鎖を合成させる。これらの温度変化を繰り返すことでＤＮＡを指数関数的に増幅させることができる。一方で、試薬が求める温度に対して過度な温度上昇や温度降下が生じると、目標としているＤＮＡが増幅しないといった課題が生じるため、高精度な温度制御が求められる。　
　さらに、遺伝子検査に必要な試料や試薬の定量、攪拌といった操作を自動化するため、使い捨ての基板上で送液を実現する流路チップの開発が進められており、流路チップ表面に設けた弾性膜の変形を利用して送液するチップが報告されている。さらに送液した後に送液チップ上でＰＣＲ法を実現させるため、ペルチェ素子を用いて温度変化を与える構造の開発が進められている。 In recent years, genetic tests have come to be used not only for research purposes but also for a wide range of purposes such as personalized medicine and identification for identifying individuals, and not only accuracy but also shortening of test time is desired. When conducting a genetic test, a sample containing DNA (Deoxyribonucleic acid, deoxyribonucleic acid) is obtained, and then a small amount of DNA in the sample is amplified and then analyzed to realize highly accurate analysis. Here, as a method for amplifying DNA, a PCR (Polymerase Chain Reaction, polymerase chain reaction) method is widely used. In the PCR method, a sample solution containing DNA and a solution containing a reagent for amplifying DNA are mixed, denatured into a single strand at 94°C, and a complementary strand is synthesized at 60°C. By repeating these temperature changes, DNA can be amplified exponentially. On the other hand, when the temperature rises or falls excessively with respect to the temperature required by the reagent, a problem that the target DNA is not amplified occurs, so that highly accurate temperature control is required.
Furthermore, in order to automate operations such as quantification and stirring of samples and reagents required for genetic testing, the development of a flow path chip that realizes liquid transfer on a disposable substrate is underway, and the elasticity provided on the surface of the flow path chip. It has been reported that a chip is delivered by utilizing deformation of a membrane. Further, in order to realize the PCR method on the liquid feeding chip after the liquid is fed, the development of a structure for giving a temperature change using a Peltier element is underway.
　一方で、流路チップに設けた送液を制御する弾性膜を介して溶液を温度変化させる場合、弾性膜と温度制御装置が適切に接触していなければ、弾性膜と温度制御装置の間に生じる接触熱抵抗が増大することで、温度制御装置と溶液間の温度差が増大し、ＰＣＲ法で求められる温度に制御することが困難になる。溶液が適切な温度に制御されない場合、安定したＤＮＡの増幅を行うことができず、遺伝子検査装置の信頼性が低下するといった課題がある。　
　これらの課題に対して、温度制御部と弾性膜間の接触熱抵抗を低減させる構造が検討されており、例えば特許文献１では、液体試料を収容する容器部の内部に対して圧力を加えながら、液体試料を加熱する方式が開示されている。また、特許文献２には、上部硬質基板と、メンブレン層と、台座基板と、開口部を有する凹陥部が形成された少なくとも１個の支持カップ基板を有する構成が記載されている。 On the other hand, when the temperature of the solution is changed through the elastic film that controls the liquid transfer provided in the channel chip, if the elastic film and the temperature control device are not in proper contact, the elastic film and the temperature control device are not The increased contact thermal resistance increases the temperature difference between the temperature control device and the solution, making it difficult to control the temperature required by the PCR method. If the solution is not controlled to an appropriate temperature, stable DNA amplification cannot be performed, and there is a problem that the reliability of the genetic test device is reduced.
To solve these problems, a structure for reducing the contact thermal resistance between the temperature control unit and the elastic film has been studied. For example, in Patent Document 1, while applying pressure to the inside of the container unit that stores the liquid sample. , A method of heating a liquid sample is disclosed. Further, Patent Document 2 describes a configuration including an upper hard substrate, a membrane layer, a pedestal substrate, and at least one support cup substrate having a recess having an opening formed therein.
ＷＯ２０１２／０８６１６８号公報WO2012/086168 特開２０１１－３０５２２号公報Japanese Unexamined Patent Publication No. 2011-30522
　特許文献１では、メンブレンと基板で封止された溶液に対して圧力を印加することで、温度制御ブロックに溶液を、メンブレンを介して押しつけ、温度制御ブロックとの熱交換効率を高めている。しかし、特許文献１に記載された温度制御構造では、溶液の温調を行う反応容器部に圧力を加える機構が必要であり送液機構が複雑になる、また、メンブレンは温度変化に伴い熱変形を生じ、この熱変形に伴って接触熱抵抗が変化するため、一様かつ高精度な温度変化を与えることが困難であるという課題がある。また、特許文献２においても、メンブレンは温度変化に伴い熱変形を生じ、この熱変形に伴って接触熱抵抗が変化するため、一様かつ高精度な温度変化を与えることが困難である。 In Patent Document 1, by applying pressure to the solution sealed with the membrane and the substrate, the solution is pressed against the temperature control block through the membrane, and the heat exchange efficiency with the temperature control block is improved. However, the temperature control structure described in Patent Document 1 requires a mechanism for applying pressure to the reaction container portion that controls the temperature of the solution, which complicates the liquid feeding mechanism. Further, the membrane undergoes thermal deformation with temperature change. Occurs, and the contact thermal resistance changes due to this thermal deformation, so there is a problem that it is difficult to give a uniform and highly accurate temperature change. Further, also in Patent Document 2, the membrane undergoes thermal deformation with a temperature change, and the contact thermal resistance changes with the thermal deformation, so that it is difficult to give a uniform and highly accurate temperature change.
　そこで本発明は、熱変形による接触熱抵抗の悪化を抑制し、高速かつ高精度な温度制御装置用送液カートリッジを提供する。 Therefore, the present invention provides a high-speed and highly accurate liquid-feeding cartridge for a temperature control device, which suppresses deterioration of contact thermal resistance due to thermal deformation.
　上記課題を解決するため、本発明に係る温度制御装置用送液カートリッジは、温度調整部に配され得る第２の層と、前記第２の層との間隙にて流路を形成する送液チップと、前記温度調整部の領域外において、前記第２の層より前記送液チップの側である上側、又は、前記第２の層の下側に配され、弾性体からなり、且つ、前記第２の層よりも線膨張係数が大きい第１の層と、を備えることを特徴とする。 In order to solve the above problems, the liquid feeding cartridge for a temperature control device according to the present invention is a liquid feeding cartridge that forms a flow path in a gap between a second layer that can be arranged in a temperature adjusting unit and the second layer. Outside the region of the chip and the temperature adjusting unit, the liquid transfer chip is arranged on the upper side of the second layer or on the lower side of the second layer, and is made of an elastic body. A first layer having a linear expansion coefficient larger than that of the second layer.
　また、本発明に係る他の温度制御装置用送液カートリッジは、温度調整部に配され得る第２の層と、前記第２の層との間隙にて流路を形成する送液チップと、前記第２の層より前記送液チップとは反対側である下側に配され、弾性体からなり、且つ、前記第２の層よりも線膨張係数が大きい第１の層と、を備えることを特徴とする。 Further, another liquid feeding cartridge for a temperature control device according to the present invention includes a liquid feeding tip that forms a flow path in a gap between a second layer that can be arranged in the temperature control unit and the second layer. A first layer which is disposed on the lower side of the second layer, which is the side opposite to the liquid delivery chip, and which is made of an elastic body and has a linear expansion coefficient larger than that of the second layer. It is characterized by.
　本発明によれば、熱変形による接触熱抵抗の悪化を抑制し、高速かつ高精度な温度制御装置用送液カートリッジを提供することが可能となる。　
　上記した以外の課題、構成及び効果は、以下の実施形態の説明により明らかにされる。 ADVANTAGE OF THE INVENTION According to this invention, it becomes possible to suppress the deterioration of contact thermal resistance due to thermal deformation, and to provide a high-speed and highly accurate liquid feeding cartridge for a temperature control device.
Problems, configurations, and effects other than those described above will be clarified by the following description of the embodiments.
本発明の一実施例に係る実施例１による温度制御装置の概略上面図である。FIG. 3 is a schematic top view of a temperature control device according to a first embodiment of the present invention. 実施例１による温度制御装置の概略側面図である。3 is a schematic side view of the temperature control device according to the first embodiment. FIG. 図１及び図２に示す送液カートリッジの構成図である。It is a block diagram of the liquid feeding cartridge shown in FIG. 1 and FIG. 図１における温度制御装置の構造を説明するＡ－Ａ’断面図である。FIG. 2 is a cross-sectional view taken along the line A-A′ for explaining the structure of the temperature control device in FIG. 1. 図１における温度制御装置の構造を説明するＢ－Ｂ’断面図である。FIG. 2 is a B-B′ cross-sectional view illustrating the structure of the temperature control device in FIG. 1. 実施例１による送液カードリッジの溶液導入状態を示す図である。FIG. 3 is a diagram showing a solution introduction state of a liquid-feeding cartridge according to Example 1. 実施例１による送液カードリッジの流路密閉状態を示す図である。FIG. 3 is a diagram showing a flow path hermetically sealed state of a liquid delivery cartridge according to the first embodiment. 実施例１による送液カードリッジの溶液を温調流路に保持した状態を示す図である。FIG. 3 is a diagram showing a state in which a solution of a liquid-fed cartridge according to Example 1 is held in a temperature control channel. 実施例１による送液カードリッジの溶液の温調流路からの移動状態を示す図である。FIG. 6 is a diagram showing a movement state of a solution of a liquid-fed cartridge according to Example 1 from a temperature control channel. 実施例１による送液カードリッジの溶液排出状態を示す図である。FIG. 3 is a diagram showing a solution discharge state of a liquid-feeding cartridge according to the first embodiment. 本発明の他の実施例に係る実施例２による温度制御装置の構造を説明する断面図である。It is sectional drawing explaining the structure of the temperature control apparatus by Example 2 which concerns on the other Example of this invention. 図７の変形例を示す図である。It is a figure which shows the modification of FIG. 本発明の他の実施例に係る実施例３による温度制御装置の構造を説明する断面図である。It is sectional drawing explaining the structure of the temperature control apparatus by Example 3 which concerns on the other Example of this invention. 本発明の他の実施例に係る実施例４による温度制御装置の構造を説明する断面図である。It is sectional drawing explaining the structure of the temperature control apparatus by Example 4 which concerns on the other Example of this invention. 本発明の他の実施例に係る実施例５による温度制御装置の構造を説明する断面図である。It is sectional drawing explaining the structure of the temperature control apparatus by Example 5 which concerns on the other Example of this invention.
　本発明の送液カートリッジを適用する「化学分析装置」としては、ＤＮＡ解析装置、核酸増幅装置、遺伝子検査装置が含まれる。　
　以下、図面を用いて本発明の実施例について説明する。 The “chemical analysis device” to which the liquid delivery cartridge of the present invention is applied includes a DNA analysis device, a nucleic acid amplification device, and a gene test device.
Embodiments of the present invention will be described below with reference to the drawings.
　図１は本発明の一実施例に係る実施例１による温度制御装置２０の概略上面図である。また、図２は温度制御装置２０の概略側面図である。なお、図１では、送液カートリッジ１と送液制御部５によって形成される流路形状を破線で示している。図２に示すように、温度制御装置２０は、送液カートリッジ１、送液制御部５、及び温調部１６から構成される。図３は送液カートリッジ１を構成する各層の構造を示している。送液カートリッジ１は、送液チップ２と弾性体からなる第１の層４と、第１の層よりも線膨張係数が小さい材料から成る第２の層３から構成され、送液制御部５の上面に固定される。なお、送液カートリッジ１は、送液制御部５の上面に対し着脱自在である。送液チップ２は、溶液を導入する導入孔１０と、溶液を排出する排出孔１１が形成されている。送液チップ２の底面に溝を形成し、流路８と温調流路８ａとする。導入孔１０と排出孔１１は送液チップ２の上面から下面まで連通しており、流路８と温調流路８ａを通じて溶液を移動させることができる。第２の層３は送液制御部５に形成する第１の送液弁９ａと第２の送液弁９ｂ、第３の送液弁９ｃと略同一形状の開口部３ａを有する。第１の層４は温調流路８ａと略同一形状の開口部４ａを有する。送液制御部５は温調部１６を固定するための開口部９ｄと、第１の送液弁９ａと第２の送液弁９ｂ、第３の送液弁９ｃとなる凹部が形成される。さらに第１の送液弁９ａと第２の送液弁９ｂ、第３の送液弁９ｃの底面には貫通孔１２が形成される。また、貫通孔１２は流体例えば空気の導入、排出を制御する装置（図示せず）と接続される。図４は図１に示した温度制御装置２０におけるＡ－Ａ’方向の断面図を示している。送液カートリッジ１の底面に送液制御部５と、温調部１６が固定される。ここで、温調部１６を構成する温度制御ブロック６は、第１の層４に形成した開口部４ａ（図３）を介して第２の層３に接触し、送液チップ２の温調流路８ａの底面に固定される。送液制御部５に形成した第１の層４は温度制御ブロック６に接触しない。第２の層３は、第１の送液弁９ａと第２の送液弁９ｂ、第３の送液弁９ｃと略同一の開口部３ａを有しており、開口部３ａと送液弁の位置が一致するように貼り合わせる。そのため、送液弁の開口部上部には第２の層３は形成されない。図５は温度制御装置２０におけるＢ－Ｂ’方向の断面図を示す。送液チップ２に形成した温調流路８ａの底面は第２の層３が配置され、第１の層４に形成された開口部４ａを介して温度制御ブロック６に押圧されることで温調流路８ａの底面を密閉する。 FIG. 1 is a schematic top view of the temperature control device 20 according to the first embodiment according to the first embodiment of the present invention. Further, FIG. 2 is a schematic side view of the temperature control device 20. In FIG. 1, the shape of the flow path formed by the liquid feed cartridge 1 and the liquid feed control unit 5 is shown by a broken line. As shown in FIG. 2, the temperature control device 20 includes a liquid feed cartridge 1, a liquid feed control unit 5, and a temperature control unit 16. FIG. 3 shows the structure of each layer constituting the liquid feeding cartridge 1. The liquid feed cartridge 1 is composed of a first layer 4 made of a liquid feed tip 2 and an elastic body, and a second layer 3 made of a material having a coefficient of linear expansion smaller than that of the first layer, and is composed of a liquid feed control unit 5. Fixed on the upper surface of. The liquid feed cartridge 1 is removable from the upper surface of the liquid feed control unit 5. The liquid-feeding chip 2 has an introduction hole 10 for introducing a solution and a discharge hole 11 for discharging the solution. A groove is formed on the bottom surface of the liquid feeding tip 2 to form a flow path 8 and a temperature control flow path 8a. The introduction hole 10 and the discharge hole 11 communicate with each other from the upper surface to the lower surface of the liquid feeding chip 2, and the solution can be moved through the channel 8 and the temperature control channel 8a. The second layer 3 has an opening 3a having substantially the same shape as the first liquid feeding valve 9a, the second liquid feeding valve 9b, and the third liquid feeding valve 9c formed in the liquid feeding control unit 5. The first layer 4 has an opening 4a having substantially the same shape as the temperature control flow path 8a. The liquid feed control unit 5 is formed with an opening 9d for fixing the temperature control unit 16 and recesses serving as a first liquid feed valve 9a, a second liquid feed valve 9b, and a third liquid feed valve 9c. .. Further, through holes 12 are formed in the bottom surfaces of the first liquid feeding valve 9a, the second liquid feeding valve 9b, and the third liquid feeding valve 9c. Further, the through hole 12 is connected to a device (not shown) that controls the introduction and discharge of a fluid such as air. FIG. 4 shows a cross-sectional view of the temperature control device 20 shown in FIG. 1 in the AA'direction. The liquid feed control unit 5 and the temperature control unit 16 are fixed to the bottom surface of the liquid feed cartridge 1. Here, the temperature control block 6 constituting the temperature control unit 16 contacts the second layer 3 through the opening 4a (FIG. 3) formed in the first layer 4, and the temperature control of the liquid feeding tip 2 is performed. It is fixed to the bottom surface of the channel 8a. The first layer 4 formed in the liquid feed control unit 5 does not come into contact with the temperature control block 6. The second layer 3 has an opening 3a substantially the same as the first liquid feeding valve 9a, the second liquid feeding valve 9b, and the third liquid feeding valve 9c, and the opening 3a and the liquid feeding valve Attach so that the positions of are the same. Therefore, the second layer 3 is not formed on the upper part of the opening of the liquid feed valve. FIG. 5 shows a cross-sectional view of the temperature control device 20 in the BB'direction. The second layer 3 is disposed on the bottom surface of the temperature control channel 8a formed in the liquid feeding chip 2, and the temperature is controlled by being pressed by the temperature control block 6 through the opening 4a formed in the first layer 4. The bottom surface of the flow control channel 8a is sealed.
　次に温度制御装置２０における送液制御部５を用いた液移動の例を示す。まず、図６Ａに示すように、送液チップ２の導入孔１０に溶液１３を配置する（溶液導入状態）。ここで、図６Ｂに示すように、第２の送液弁９ｂに貫通孔１２を介して空気を導入し、第１の層４を押し上げ、すなわち第２の送液弁９ｂを押し上げて、第１の層４を送液チップ２の底面に接触させることで流路８を密閉する（流路密閉状態）。ここで、第１の送液弁９ａの空気を排出することで第１の層４が変形し、すなわち第１の送液弁９ａを引き下げることで、導入孔１０に配置した溶液１３が流路８を通じて第１の送液弁９ａに吸引される。さらに図６Ｃに示すように、まず第３の送液弁９ｃを押し上げて流路８を密閉し、第２の送液弁９ｂを引き下げることで溶液１３を送液チップ２における温調流路８ａに引き込み、さらに第１の送液弁９ａを押し上げて流路８を密閉し、第３の送液弁９ｃを引き下げて流路８を開放し、第２の送液弁９ｂを押し上げることで溶液１３を温調流路８ａに保持する（溶液を温調流路に保持した状態）。ここで、温調部１６を構成する温度制御素子７によって温度制御ブロック６の温度を変化させ、第２の層３を介して溶液１３に温度変化を与えることができる。温度変化の操作が完了したのち、図６Ｄに示すように第３の送液弁９ｃを押し上げて流路８を密閉し、第１の送液弁９ａと第３の送液弁９ｃを引き下げることで溶液１３が第２の送液弁９ｂの領域に進む（溶液の温調流路からの移動状態）。さらに図６Ｅに示すように、第３の送液弁９ｃを引き下げて流路８を開放し、第１の送液弁９ａと第２の送液弁９ｂを押し上げることで溶液１３を排出孔１１から押し出すことができ、温度処理を行った溶液１３を送液カートリッジ１から取り出すことができる（溶液排出状態）。 Next, an example of liquid transfer using the liquid transfer controller 5 in the temperature control device 20 will be shown. First, as shown in FIG. 6A, the solution 13 is placed in the introduction hole 10 of the liquid feeding chip 2 (solution introduction state). Here, as shown in FIG. 6B, air is introduced into the second liquid feeding valve 9b through the through hole 12 to push up the first layer 4, that is, to push up the second liquid feeding valve 9b, The channel 8 is sealed by bringing the layer 4 of No. 1 into contact with the bottom surface of the liquid-feeding chip 2 (channel closed state). Here, by discharging the air from the first liquid feed valve 9a, the first layer 4 is deformed, that is, by pulling down the first liquid feed valve 9a, the solution 13 arranged in the introduction hole 10 flows through the flow path. The liquid is sucked through the first liquid feeding valve 9 a through the valve 8. Further, as shown in FIG. 6C, first the third liquid feed valve 9c is pushed up to seal the flow path 8, and then the second liquid feed valve 9b is pulled down to transfer the solution 13 to the temperature control flow path 8a in the liquid feed tip 2. To the solution by pushing up the first liquid feed valve 9a to seal the flow passage 8, lowering the third liquid feed valve 9c to open the flow passage 8, and pushing up the second liquid feed valve 9b. 13 is held in the temperature control flow path 8a (a state in which the solution is held in the temperature control flow path). Here, the temperature of the temperature control block 6 can be changed by the temperature control element 7 that constitutes the temperature control unit 16, and the temperature of the solution 13 can be changed via the second layer 3. After the temperature change operation is completed, as shown in FIG. 6D, the third liquid feed valve 9c is pushed up to seal the flow path 8, and the first liquid feed valve 9a and the third liquid feed valve 9c are pulled down. Then, the solution 13 advances to the area of the second liquid feeding valve 9b (movement state of the solution from the temperature control channel). Further, as shown in FIG. 6E, the third liquid feed valve 9c is pulled down to open the flow path 8, and the first liquid feed valve 9a and the second liquid feed valve 9b are pushed up to discharge the solution 13 into the discharge hole 11. The solution 13 that has been subjected to the temperature treatment can be taken out from the liquid feeding cartridge 1 (solution discharge state).
　ここで、温度制御素子７よって温度を制御するために必要となる温度センサ（図示せず）を温度制御ブロック６に設置することで、所望の温度変化であることを確認することができる。例えば、ＤＮＡを含む試料と、ＤＮＡを増幅する酵素が含まれている試薬を混合し、送液カートリッジ１上の温調流路８ａに送液し、９４°Ｃと６０°Ｃに繰り返し温度変化させることで、ＤＮＡを増幅させ、分析を行うことができる。 Here, by installing a temperature sensor (not shown) required for controlling the temperature by the temperature control element 7 in the temperature control block 6, it is possible to confirm that the temperature change is a desired one. For example, a sample containing DNA and a reagent containing an enzyme that amplifies DNA are mixed, and the liquid is sent to the temperature control flow path 8a on the liquid feed cartridge 1, and the temperature is repeatedly changed to 94 ° C and 60 ° C. By so doing, the DNA can be amplified and analyzed.
　上述した本実施例により、温調流路８ａを形成する底面の熱変形は小さく、温度制御ブロック６と第２の層３の間の接触熱抵抗が一様に保たれる。そのため，温調部１６による温度変化を精度よく溶液１３に伝えることができる。本実施例によれば、温調ブロック６は熱変形の小さい第２の層３のみに接触しており、熱変形の大きい第１の層４には接触していないため、温度変化に伴う熱変形が抑えられるため、一様な接触状態が保たれ、接触熱抵抗が変化しない。 According to the above-described embodiment, the thermal deformation of the bottom surface forming the temperature control flow path 8a is small, and the contact thermal resistance between the temperature control block 6 and the second layer 3 is kept uniform. Therefore, the temperature change by the temperature adjustment unit 16 can be accurately transmitted to the solution 13. According to this embodiment, since the temperature control block 6 is in contact with only the second layer 3 having a small thermal deformation and not in contact with the first layer 4 having a large thermal deformation, the heat accompanying the temperature change is generated. Since the deformation is suppressed, a uniform contact state is maintained and the contact thermal resistance does not change.
　なお、本実施例では、流路８は送液チップ２に１系統のみ形成していたが、１系統に限定するものではなく、複数の溶液を送液、混合するために導入孔、流路、排出孔を複数有する送液チップとしてもよい。また、温度制御ブロック６は、温度制御素子７の温度変化を温調流路８ａに保持される溶液１３に効率よく伝えることを目的としているため、熱伝導率の高い金属材料であることが好ましく、たとえばアルミニウムや銅で形成することが望ましい。また、温度制御素子７はペルチェ素子や、ヒータを用いた加熱、冷却媒体を通過させることによって温度を調整する構造とすることができる。送液制御部５は空気を用いて第１の層４を変形させる構造としていたが、水やオイルを用いて第１の層４を変形させてもよい。また、第２の層３は線膨張係数が小さい材質であることが望ましく、ポリイミド、ポリエステル、テフロン（登録商標）などで形成することが望ましい。 In this embodiment, only one flow path 8 is formed in the liquid feeding tip 2, but the flow path 8 is not limited to one system, and an introduction hole and a flow path for sending and mixing a plurality of solutions. Alternatively, a liquid-feeding chip having a plurality of discharge holes may be used. Further, since the temperature control block 6 is intended to efficiently transfer the temperature change of the temperature control element 7 to the solution 13 held in the temperature control channel 8a, it is preferably a metal material having high thermal conductivity. It is desirable to form it with aluminum or copper, for example. Further, the temperature control element 7 may have a structure in which the temperature is adjusted by passing a Peltier element or heating using a heater or a cooling medium. Although the liquid transfer control unit 5 has a structure in which the first layer 4 is deformed by using air, the first layer 4 may be deformed by using water or oil. The second layer 3 is preferably made of a material having a small linear expansion coefficient, and is preferably made of polyimide, polyester, Teflon (registered trademark) or the like.
　以上の通り本実施例によれば、熱変形による接触熱抵抗の悪化を抑制し、高速かつ高精度な温度制御装置用送液カートリッジを提供することが可能となる。 As described above, according to this embodiment, it is possible to provide a high-speed and high-accuracy liquid delivery cartridge for a temperature control device, which suppresses deterioration of contact thermal resistance due to thermal deformation.
　図７は本発明の他の実施例に係る実施例２による温度制御装置の構造を説明する断面図であり、図８は図７の変形例を示す図である。本実施例では、第２の層３が粘着層１４を有する点が実施例１と異なる。その他の構成は、上述の実施例１と同様であり、以下では、実施例１と同一の構成要素に同一符号を付し、実施例１と重複する説明を省略する。 FIG. 7 is a sectional view for explaining the structure of a temperature control device according to a second embodiment of the present invention, and FIG. 8 is a view showing a modification of FIG. This example differs from Example 1 in that the second layer 3 has an adhesive layer 14. Other configurations are the same as those in the above-described first embodiment, and in the following, the same components as those in the first embodiment will be denoted by the same reference numerals and overlapping description of the first embodiment will be omitted.
　図７に示すように、粘着層１４は第２の層３の両面に形成される。ここで、粘着層１４は送液チップ２に形成する流路８、送液制御部５に形成する第１の送液弁９ａ、第２の送液弁９ｂ、第３の送液弁９ｃ部は選択的に粘着層１４が存在しない。
上述した本実施例によれば、第２の層３が送液チップ２および第１の層４と粘着層１４を介して接着され、第２の層３と送液チップ２の隙間および第１の層４と第２の層３の隙間からの液の漏れ出しや、蒸気の漏れ出しが抑制される。 As shown in FIG. 7, the adhesive layer 14 is formed on both surfaces of the second layer 3. Here, the adhesive layer 14 is a flow path 8 formed in the liquid feed chip 2, a first liquid feed valve 9a, a second liquid feed valve 9b, and a third liquid feed valve 9c formed in the liquid feed control unit 5. Selectively does not have the adhesive layer 14.
According to the present embodiment described above, the second layer 3 is adhered to the liquid-feeding chip 2 and the first layer 4 via the adhesive layer 14, and the gap between the second layer 3 and the liquid-feeding chip 2 and the first layer are provided. The leakage of the liquid and the leakage of the vapor from the gap between the layer 4 and the second layer 3 are suppressed.
　また、第２の層３が温度制御ブロック６に接着されるため、第２の層３の温度制御ブロック６への接触状態が変化せず、温度制御状態が安定する。ただし、応答性を重視する場合は、温度制御ブロック６に接触させている粘着層１４の箇所を（図８に示すように）除去し、直接第２の層３と温度制御ブロック６を接触させてもよい。 Further, since the second layer 3 is adhered to the temperature control block 6, the contact state of the second layer 3 with the temperature control block 6 does not change, and the temperature control state is stable. However, when importance is attached to the responsiveness, the portion of the adhesive layer 14 that is in contact with the temperature control block 6 is removed (as shown in FIG. 8) and the second layer 3 and the temperature control block 6 are directly contacted. You may.
　以上の通り、本実施例によれば、実施例１の効果に加え、粘着層１４により、第２の層３と送液チップ２の隙間および第１の層４と第２の層３の隙間からの液の漏れ出しや、蒸気の漏れ出しが抑制される。また、第２の層３が温度制御ブロック６に接着されるため、第２の層３の温度制御ブロック６への接触状態が変化せず、温度制御状態が安定する。 As described above, according to the present embodiment, in addition to the effect of the first embodiment, the gap between the second layer 3 and the liquid delivery chip 2 and the gap between the first layer 4 and the second layer 3 are provided by the adhesive layer 14. Leakage of liquid and steam is suppressed. Further, since the second layer 3 is adhered to the temperature control block 6, the contact state of the second layer 3 with the temperature control block 6 does not change, and the temperature control state becomes stable.
　図９は本発明の他の実施例に係る実施例３による温度制御装置の構造を説明する断面図である。本実施例では、送液チップ２における温調流路８ａの周囲に凸部１５を設けた点が実施例１と異なる。その他の構成は、上述の実施例１と同様であり、以下では、実施例１と同一の構成要素に同一符号を付し、実施例１と重複する説明を省略する。 FIG. 9 is a sectional view illustrating the structure of a temperature control device according to a third embodiment of the present invention. The present embodiment is different from the first embodiment in that the convex portion 15 is provided around the temperature control channel 8a in the liquid feeding chip 2. Other configurations are the same as those in the first embodiment, and the same components as those in the first embodiment are designated by the same reference numerals, and the description overlapping with the first embodiment will be omitted.
　図９に示すように、送液チップ２に形成した凹部によって流路８を形成するが、温調流路８ａの周囲に凸部１５を設ける。これにより、温調流路８ａの周囲のみ第２の層３を押し付ける圧力が高まり、温調流路８ａからの液の漏れ出しや、蒸気の漏れ出しを抑制することができる。ただし、温調流路８ａの周りに形成する凸部１５は１段であることに限定されるものではなく、例えば温度制御ブロック６に凹部を形成し、櫛歯型とすることでさらに押しつけ面圧を高めてもよい。 As shown in FIG. 9, the flow channel 8 is formed by the concave portion formed in the liquid feeding chip 2, and the convex portion 15 is provided around the temperature control flow channel 8a. As a result, the pressure that presses the second layer 3 only around the temperature control flow path 8a increases, and it is possible to suppress the leakage of liquid and the leakage of vapor from the temperature control flow path 8a. However, the convex portion 15 formed around the temperature control flow path 8a is not limited to a single step, and for example, a concave portion is formed in the temperature control block 6 and a comb tooth shape is formed to further press the pressing surface. The pressure may be increased.
　以上の本実施例によれば、実施例１の効果に加え、温調流路８ａからの液の漏れ出しや、蒸気の漏れ出しを抑制することができる。 According to the present embodiment described above, in addition to the effect of the first embodiment, it is possible to suppress the leakage of the liquid and the leakage of the vapor from the temperature control channel 8a.
　図１０は本発明の他の実施例に係る実施例４による温度制御装置の構造を説明する断面図である。本実施例では、送液チップ２と第１の層４を密着させ、第１の層４の下面に第２の層３を構築した点が実施例１と異なる。その他の構成は、上述の実施例１と同様であり、以下では、実施例１と同一の構成要素に同一符号を付し、実施例１と重複する説明を省略する。 FIG. 10 is a sectional view illustrating the structure of a temperature control device according to a fourth embodiment of the present invention. This embodiment is different from the first embodiment in that the liquid feeding chip 2 and the first layer 4 are brought into close contact with each other and the second layer 3 is constructed on the lower surface of the first layer 4. Other configurations are the same as those in the first embodiment, and the same components as those in the first embodiment are designated by the same reference numerals, and the description overlapping with the first embodiment will be omitted.
　図１０に示すように、送液カートリッジ１に第１の層４を密着させ、その下面に第２の層３を密着させる構造とする。すなわち、上述の実施例１と比較し、本実施例では流路８がＮＣ（ノーマリークローズ）となっている。従って、送液チップ２と弾性体から成る第１の層４を密着させることができるため、温調流路８ａからの液漏れや蒸気の漏れ出しを抑制することができる。 As shown in FIG. 10, the first layer 4 is brought into close contact with the liquid feeding cartridge 1 and the second layer 3 is brought into close contact with the lower surface thereof. That is, as compared with the above-described first embodiment, the flow path 8 is NC (normally closed) in this embodiment. Therefore, since the liquid-feeding chip 2 and the first layer 4 made of an elastic body can be brought into close contact with each other, it is possible to prevent liquid leakage and vapor leakage from the temperature control channel 8a.
　ただし、第２の層３は接着層を有してもよく、温度制御ブロック６と温調流路８ａの界面に熱伝導シートや熱伝導グリースを塗布することで界面の接触熱抵抗を低減する構造としてもよい。 However, the second layer 3 may have an adhesive layer, and by applying a heat conductive sheet or heat conductive grease to the interface between the temperature control block 6 and the temperature control channel 8a, the contact thermal resistance of the interface is reduced. It may be a structure.
　以上の通り本実施例によれば、実施例１の効果に加え、温調流路８ａからの液漏れや蒸気の漏れ出しを抑制することが可能となる。 As described above, according to the present embodiment, in addition to the effects of the first embodiment, it is possible to suppress liquid leakage and vapor leakage from the temperature control flow path 8a.
　図１１は本発明の他の実施例に係る実施例５による温度制御装置の構造を説明する断面図である。本実施例では、第１の層４を，送液制御部５のみならず温度制御ブロック６にも密着させ，さらに第２の層３を温度制御ブロック６の領域で第１の層４に密着させることで，送液チップ２との間に温調流路８ａを構築した点が実施例１と異なる。その他の構成は、上述の実施例１と同様であり、以下では、実施例１と同一の構成要素に同一符号を付し、実施例１と重複する説明を省略する。 FIG. 11 is a sectional view for explaining the structure of a temperature control device according to a fifth embodiment of the present invention. In the present embodiment, the first layer 4 is brought into close contact not only with the liquid delivery control unit 5 but also with the temperature control block 6, and further the second layer 3 is brought into close contact with the first layer 4 in the region of the temperature control block 6. By doing so, the point that the temperature control flow path 8a is constructed between the liquid sending chip 2 and the first embodiment is different. Other configurations are the same as those in the first embodiment, and the same components as those in the first embodiment are designated by the same reference numerals, and the description overlapping with the first embodiment will be omitted.
　図１１に示すように、第１の層４を，送液制御部５だけでなく温度制御ブロック６にも密着させ，さらに第２の層３を温度制御ブロック６の領域で第１の層４に密着させる構造とする。すなわち、上述の実施例１と比較し、本実施例では第１の層４には温調流路８ａと略同一形状の開口部４ａ（図３）を設けず，第１の層４には開口部がない。そのため，温調流路８ａからの外部への液漏れや蒸気の漏れ出しを防止することができる。 As shown in FIG. 11, the first layer 4 is brought into close contact not only with the liquid delivery control unit 5 but also with the temperature control block 6, and the second layer 3 is further applied in the region of the temperature control block 6. The structure is such that it is in close contact with. That is, as compared with the above-described first embodiment, in the present embodiment, the first layer 4 is not provided with the opening 4a (FIG. 3) having substantially the same shape as the temperature control channel 8a, and the first layer 4 is not provided. There is no opening. Therefore, it is possible to prevent liquid leakage or vapor leakage from the temperature control flow path 8a to the outside.
　とくに，第２の層３を温調制御ブロック６の領域に限定した場合は，温調流路８ａの周辺は，第２の層３と送液チップ２とが密着するため，液漏れや蒸気の漏れ出しを防止することができる。 In particular, when the second layer 3 is limited to the region of the temperature control block 6, the second layer 3 and the liquid delivery chip 2 are in close contact with each other in the vicinity of the temperature control flow path 8a, so that liquid leakage or vapor is generated. Can be prevented from leaking.
　以上の通り本実施例によれば、実施例１の効果に加え、温調流路８ａからの液漏れや蒸気の漏れ出しを防止することが可能となる。 As described above, according to the present embodiment, in addition to the effects of the first embodiment, it becomes possible to prevent liquid leakage and vapor leakage from the temperature control channel 8a.
　なお、本発明は上記した実施例に限定されるものではなく、様々な変形例が含まれる。例えば、上記した実施例は本発明を分かりやすく説明するために詳細に説明したものであり、必ずしも説明した全ての構成を備えるものに限定されるものではない。また、ある実施例の構成の一部を他の実施例の構成に置き換えることが可能であり、また、ある実施例の構成に他の実施例の構成を加えることも可能である。また、各実施例の構成の一部について、他の実施例の構成の追加・削除・置換をすることが可能である。 It should be noted that the present invention is not limited to the above-described embodiments, but includes various modifications. For example, the above-described embodiments have been described in detail in order to explain the present invention in an easy-to-understand manner, and are not necessarily limited to those having all the configurations described. Further, a part of the configuration of one embodiment can be replaced with the configuration of another embodiment, and the configuration of another embodiment can be added to the configuration of one embodiment. Further, with respect to a part of the configuration of each embodiment, it is possible to add/delete/replace the configuration of another embodiment.
１…送液カートリッジ、２…送液チップ、３…第２の層、４…第１の層、５…送液制御部、６…温度制御ブロック、７…温度制御素子、８…流路、８ａ…温調流路、９ａ…第１の送液弁、９ｂ…第２の送液弁、９ｃ…第３の送液弁、１０…導入孔、１１…排出孔、１２…空気流路、１３…溶液、１４…粘着層、１５…凸部、１６…温調部、２０…温度制御装置 1 ... Liquid feed cartridge, 2 ... Liquid feed chip, 3 ... Second layer, 4 ... First layer, 5 ... Liquid feed control unit, 6 ... Temperature control block, 7 ... Temperature control element, 8 ... Flow path, 8a... Temperature control flow path, 9a... First liquid feed valve, 9b... Second liquid feed valve, 9c... Third liquid feed valve, 10... Introduction hole, 11... Discharge hole, 12... Air flow path, 13... Solution, 14... Adhesive layer, 15... Convex part, 16... Temperature control part, 20... Temperature control device

Claims (7)

  1. 　温度調整部に配され得る第２の層と、
    　前記第２の層との間隙にて流路を形成する送液チップと、
    　前記温度調整部の領域外において、前記第２の層より前記送液チップの側である上側、又は、前記第２の層の下側に配され、弾性体からなり、且つ、前記第２の層よりも線膨張係数が大きい第１の層と、を備えることを特徴とする温度制御装置用送液カートリッジ。     A second layer that may be disposed on the temperature control unit;
    A liquid-feeding chip that forms a flow path in the gap with the second layer;
    Outside the region of the temperature adjusting unit, the second layer is disposed on the upper side of the liquid feeding chip side or on the lower side of the second layer and is made of an elastic body, and the second layer is formed. A first layer having a linear expansion coefficient larger than that of the layer, and a liquid-feeding cartridge for a temperature control device.
  2. 　温度調整部に配され得る第２の層と、
    　前記第２の層との間隙にて流路を形成する送液チップと、
    　前記第２の層より前記送液チップとは反対側である下側に配され、弾性体からなり、且つ、前記第２の層よりも線膨張係数が大きい第１の層と、を備えることを特徴とする温度制御装置用送液カートリッジ。     A second layer that may be disposed on the temperature control unit;
    A liquid-feeding chip that forms a flow path in the gap with the second layer;
    A first layer which is disposed on the lower side of the second layer, which is the side opposite to the liquid delivery chip, and which is made of an elastic body and has a linear expansion coefficient larger than that of the second layer. A liquid feeding cartridge for a temperature control device, which is characterized by:
  3. 　請求項１又は請求項２に記載の温度制御装置用送液カートリッジにおいて、
    　前記第１の層と前記第２の層と前記送液チップにより送液カートリッジを形成し、前記送液カートリッジは送液制御部の上面に対し着脱自在であることを特徴とする温度制御装置用送液カートリッジ。     The liquid feeding cartridge for temperature control device according to claim 1 or 2,
    A temperature control device, wherein a liquid feeding cartridge is formed by the first layer, the second layer, and the liquid feeding chip, and the liquid feeding cartridge is attachable to and detachable from an upper surface of a liquid feeding control unit. Liquid transfer cartridge.
  4. 　請求項３に記載の温度制御装置用送液カートリッジにおいて、
    　前記送液チップは流路と温調流路の異なる流路を有し、
    　前記第２の層は、前記第２の層と前記送液チップの流路とが重なる領域において開口部を有し、
    　前記送液チップ、前記第２の層、前記第１の層の順に積層されていることを特徴とする温度制御装置用送液カートリッジ。     The liquid feeding cartridge for the temperature control device according to claim 3,
    The liquid-feeding chip has a flow path and a different temperature control flow path,
    The second layer has an opening in a region where the second layer and the flow path of the liquid delivery chip overlap each other,
    A liquid-feeding cartridge for a temperature control device, wherein the liquid-feeding chip, the second layer, and the first layer are laminated in this order.
  5. 　請求項３に記載の温度制御装置用送液カートリッジにおいて、
    　前記第２の層は、その両面に粘着層を有することを特徴とする温度制御装置用送液カートリッジ。     The liquid feeding cartridge for the temperature control device according to claim 3,
    The liquid feeding cartridge for a temperature control device, wherein the second layer has adhesive layers on both sides thereof.
  6. 　請求項３に記載の温度制御装置用送液カートリッジにおいて、
    　前記第２の層は、その両面に粘着層を有し、
    　前記粘着層は、前記温度調整部に対応する領域では除去されていることを特徴とする温度制御装置用送液カートリッジ。     The liquid feeding cartridge for the temperature control device according to claim 3,
    The second layer has an adhesive layer on both sides thereof,
    The liquid feeding cartridge for a temperature control device, wherein the adhesive layer is removed in a region corresponding to the temperature adjusting unit.
  7. 　請求項４に記載の温度制御装置用送液カートリッジにおいて、
    　前記送液チップの温調流路の周囲に凸部を有し、当該凸部が前記第２の層を押圧することを特徴とする温度制御装置用送液カートリッジ。     The liquid feeding cartridge for the temperature control device according to claim 4,
    A liquid-feeding cartridge for a temperature control device, which has a convex portion around the temperature control channel of the liquid-feeding chip, and the convex portion presses the second layer.
PCT/JP2019/009059 2019-03-07 2019-03-07 Liquid-feeding cartridge for temperature-controlling apparatuses WO2020179053A1 (en)

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