JP7549358B2 - Chip for generating thermal convection and reaction method - Google Patents

Chip for generating thermal convection and reaction method Download PDF

Info

Publication number
JP7549358B2
JP7549358B2 JP2021534010A JP2021534010A JP7549358B2 JP 7549358 B2 JP7549358 B2 JP 7549358B2 JP 2021534010 A JP2021534010 A JP 2021534010A JP 2021534010 A JP2021534010 A JP 2021534010A JP 7549358 B2 JP7549358 B2 JP 7549358B2
Authority
JP
Japan
Prior art keywords
thermal convection
liquid
inlet
rotor
generating chip
Prior art date
Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
Active
Application number
JP2021534010A
Other languages
Japanese (ja)
Other versions
JPWO2021015145A5 (en
JPWO2021015145A1 (en
Inventor
直哉 井上
大介 甲田
博 秋山
良彰 植森
真人 齋藤
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
Osaka University NUC
Original Assignee
Osaka University NUC
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by Osaka University NUC filed Critical Osaka University NUC
Publication of JPWO2021015145A1 publication Critical patent/JPWO2021015145A1/ja
Publication of JPWO2021015145A5 publication Critical patent/JPWO2021015145A5/ja
Application granted granted Critical
Publication of JP7549358B2 publication Critical patent/JP7549358B2/en
Active legal-status Critical Current
Anticipated expiration legal-status Critical

Links

Images

Classifications

    • CCHEMISTRY; METALLURGY
    • C12BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12MAPPARATUS 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
    • C12M1/00Apparatus for enzymology or microbiology
    • CCHEMISTRY; METALLURGY
    • C12BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12MAPPARATUS 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
    • C12M1/00Apparatus for enzymology or microbiology
    • C12M1/34Measuring or testing with condition measuring or sensing means, e.g. colony counters
    • CCHEMISTRY; METALLURGY
    • C12BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12QMEASURING OR TESTING PROCESSES INVOLVING ENZYMES, NUCLEIC ACIDS OR MICROORGANISMS; COMPOSITIONS OR TEST PAPERS THEREFOR; PROCESSES OF PREPARING SUCH COMPOSITIONS; CONDITION-RESPONSIVE CONTROL IN MICROBIOLOGICAL OR ENZYMOLOGICAL PROCESSES
    • C12Q1/00Measuring or testing processes involving enzymes, nucleic acids or microorganisms; Compositions therefor; Processes of preparing such compositions
    • C12Q1/68Measuring or testing processes involving enzymes, nucleic acids or microorganisms; Compositions therefor; Processes of preparing such compositions involving nucleic acids
    • C12Q1/6844Nucleic acid amplification reactions
    • C12Q1/686Polymerase chain reaction [PCR]
    • GPHYSICS
    • G01MEASURING; TESTING
    • G01NINVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N35/00Automatic analysis not limited to methods or materials provided for in any single one of groups G01N1/00 - G01N33/00; Handling materials therefor
    • GPHYSICS
    • G01MEASURING; TESTING
    • G01NINVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N37/00Details not covered by any other group of this subclass
    • BPERFORMING OPERATIONS; TRANSPORTING
    • B01PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01LCHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
    • B01L2400/00Moving or stopping fluids
    • B01L2400/04Moving fluids with specific forces or mechanical means
    • B01L2400/0403Moving fluids with specific forces or mechanical means specific forces
    • B01L2400/0442Moving fluids with specific forces or mechanical means specific forces thermal energy, e.g. vaporisation, bubble jet
    • B01L2400/0445Natural or forced convection

Landscapes

  • Chemical & Material Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Health & Medical Sciences (AREA)
  • Engineering & Computer Science (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Organic Chemistry (AREA)
  • Wood Science & Technology (AREA)
  • Zoology (AREA)
  • Biochemistry (AREA)
  • Biotechnology (AREA)
  • General Health & Medical Sciences (AREA)
  • Analytical Chemistry (AREA)
  • Physics & Mathematics (AREA)
  • General Engineering & Computer Science (AREA)
  • Immunology (AREA)
  • Genetics & Genomics (AREA)
  • Microbiology (AREA)
  • General Physics & Mathematics (AREA)
  • Medicinal Chemistry (AREA)
  • Biomedical Technology (AREA)
  • Sustainable Development (AREA)
  • Pathology (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Proteomics, Peptides & Aminoacids (AREA)
  • Biophysics (AREA)
  • Molecular Biology (AREA)
  • Automatic Analysis And Handling Materials Therefor (AREA)

Description

本発明は、熱対流生成用チップ及び反応方法に関する。 The present invention relates to a chip for generating thermal convection and a reaction method.

遺伝子増幅方法として、ポリメラーゼ連鎖反応(Polymerase Chain Reaction、以下「PCR」と略す。)が知られている。PCRは、極めて微量のDNAサンプルから特定のDNA断片を短時間に大量に増幅できる方法であり、基礎研究のみならず、臨床遺伝子診断から食品衛生検査、犯罪捜査に至るまで、幅広い分野で利用されている。
PCRを促進する方法として、熱対流PCRが提案されている。特許文献1には、遠心促進型熱対流PCRを行うための円環流路を有するディスク状マイクロ流路チップが開示されている。
同文献に記載の熱対流生成用チップにあっては、溶液導入口(同文献中「受入部121」)が3つあり、ひとつは検体液、ひとつはPCR液、ひとつは蒸発抑制用液体(ミネラルオイル)が導入される。そこからマイクロ流路(同文献中「引通路122」)が伸長してV字型流路形状をしていて、下流側に溶液を貯える秤量用空間領域(同文献中「第1領域122a」)がある。検体液用領域とPCR液用領域の容量を合わせると円環流路(同文献中「熱対流用流路11」)と同容量になる。導入口(同文献中「受入部121」)から導入された各液体は、マイクロ流路内を毛細管現象によって進入して秤量用空間領域を満たす。このとき遠心することによってV字構造の谷部を起点に、秤量用領域の液体が円環流路に移送され、また余剰分は導入口側にもどることで円環流路に必要な容量の液体が供給される。また、秤量用V字型流路が複数配置され、それぞれ分岐した下流に円環流路を配置させることで、一つの検体に対して複数種の遺伝子を検出することができる。
Polymerase Chain Reaction (hereinafter referred to as "PCR") is a known method for amplifying genes. PCR is a method that can amplify a large amount of a specific DNA fragment from an extremely small amount of DNA sample in a short period of time, and is used in a wide range of fields, from basic research to clinical genetic diagnosis, food hygiene inspection, and criminal investigation.
Thermal convection PCR has been proposed as a method for accelerating PCR. Patent Document 1 discloses a disk-shaped microchannel chip having an annular channel for performing centrifugally accelerated thermal convection PCR.
In the thermal convection generating chip described in the same document, there are three solution inlet ports (receptor 121 in the same document), one for introducing sample liquid, one for introducing PCR liquid, and one for introducing evaporation suppression liquid (mineral oil). From there, a microchannel (inlet passage 122 in the same document) extends to form a V-shaped channel, and a weighing space region (first region 122a in the same document) for storing the solution is located downstream. The combined capacity of the sample liquid region and the PCR liquid region is the same as that of the annular channel (thermal convection channel 11 in the same document). Each liquid introduced from the inlet port (receptor 121 in the same document) enters the microchannel by capillary action and fills the weighing space region. At this time, by centrifuging, the liquid in the weighing region is transferred to the annular channel starting from the valley of the V-shaped structure, and the excess returns to the inlet side, thereby supplying the required volume of liquid to the annular channel. Furthermore, by arranging a plurality of V-shaped measuring channels and arranging circular channels downstream of each branch, it is possible to detect a plurality of types of genes from one sample.

国際公開第2015/170753号International Publication No. 2015/170753

しかし以上の従来技術にあっては、溶液導入から遠心促進型熱対流PCRを行うまでの各段階において、マイクロ流路中の液体を予定した領域に流動、安定させて制御するにはさらなる改良の余地があり、熱対流用流路への液体供給量に過不足が生じる恐れがあった。 However, in the above conventional technologies, there is room for further improvement in controlling the flow and stability of the liquid in the microchannel to the intended area at each stage from the introduction of the solution to performing centrifugally enhanced thermal convection PCR, and there was a risk of excess or deficiency in the amount of liquid supplied to the thermal convection channel.

本発明は以上の従来技術における問題に鑑みてなされたものであって、熱対流用流路への液体供給量の精度を向上することを課題とする。The present invention has been made in consideration of the problems in the conventional technology described above, and its objective is to improve the accuracy of the amount of liquid supplied to the thermal convection flow path.

本発明の第1態様は、熱対流用流路、導入口及び供給路が形成された回転体を備え、前記導入口に導入された液体を前記供給路により前記熱対流用流路に供給し前記熱対流用流路で熱対流させる熱対流生成用チップであって、前記回転体に、前記導入口に連通する液体受容部が形成され、前記液体受容部の内側面と内底面とが鋭角を成して接し、前記供給路は、前記液体受容部の前記内底面上に底辺を配置して前記内側面に開口した液体流入口を有する。 A first aspect of the present invention is a thermal convection generating chip comprising a rotor in which a thermal convection flow path, an inlet, and a supply path are formed, and liquid introduced into the inlet is supplied to the thermal convection flow path by the supply path and thermally convected in the thermal convection flow path, wherein the rotor is formed with a liquid receiving portion that communicates with the inlet, the inner side and inner bottom surface of the liquid receiving portion meet at an acute angle, and the supply path has a liquid inlet that opens to the inner side surface with its base positioned on the inner bottom surface of the liquid receiving portion.

また本発明の第2態様は、熱対流用流路、導入口及び供給路が形成された回転体を備え、前記導入口に導入された液体を前記供給路により前記熱対流用流路に供給し前記熱対流用流路で熱対流させる熱対流生成用チップであって、前記回転体に、前記導入口に連通する液体受容部が形成され、前記供給路は、前記液体受容部内の液体を毛細管現象により吸引する吸引通路を有し、前記吸引通路は、秤量空間を有し、前記吸引通路は、前記回転体を回転させたときの遠心力により、前記秤量空間内の液体が他の領域内の液体から分離して前記熱対流用流路に供給されよう構成され、前記秤量空間の前記熱対流用流路側の出口は、当該出口の縁を前記回転体が形成する平面の縁から離間して当該平面に開口している。A second aspect of the present invention is a thermal convection generating chip that includes a rotor having a thermal convection flow path, an inlet, and a supply path formed therein, and that supplies liquid introduced into the inlet to the thermal convection flow path through the supply path and causes thermal convection in the thermal convection flow path, wherein the rotor is formed with a liquid receiving portion that communicates with the inlet, the supply path has a suction passage that draws in the liquid in the liquid receiving portion by capillary action, the suction passage has a weighing space, and the suction passage is configured such that, due to centrifugal force generated when the rotor is rotated, the liquid in the weighing space is separated from the liquid in other regions and supplied to the thermal convection flow path, and the outlet of the weighing space on the thermal convection flow path side is open to the plane formed by the rotor with the edge of the outlet spaced apart from the edge of the plane.

また本発明の第3の態様は、熱対流用流路、導入口及び供給路が形成された回転体を備え、前記導入口に導入された液体を前記供給路により前記熱対流用流路に供給し前記熱対流用流路で熱対流させる熱対流生成用チップであって、前記回転体に、前記導入口に連通する液体受容部が形成され、前記供給路は、前記液体受容部内の液体を毛細管現象により吸引する吸引通路を有し、前記吸引通路は、秤量空間を有し、前記吸引通路は、前記回転体を回転させたときの遠心力により、前記秤量空間内の液体が他の領域内の液体から分離して前記熱対流用流路に供給されよう構成され、前記遠心力により前記秤量空間内の液体から分離した液体が貯留される余剰液貯留部が、前記回転体に形成されている。A third aspect of the present invention is a thermal convection generating chip that includes a rotor having a thermal convection flow path, an inlet, and a supply path formed therein, and that supplies liquid introduced into the inlet to the thermal convection flow path through the supply path and causes thermal convection in the thermal convection flow path, wherein the rotor is formed with a liquid receiving section that communicates with the inlet, the supply path has a suction passage that draws in the liquid in the liquid receiving section by capillary action, the suction passage has a weighing space, and the suction passage is configured so that the liquid in the weighing space is separated from the liquid in other areas by centrifugal force generated when the rotor is rotated and is supplied to the thermal convection flow path, and an excess liquid storage section in which liquid separated from the liquid in the weighing space by the centrifugal force is stored is formed in the rotor.

また本発明の第4の態様は、熱対流用流路、導入口及び供給路が形成された回転体を備え、前記導入口に導入された液体を前記供給路により前記熱対流用流路に供給し前記熱対流用流路で熱対流させる熱対流生成用チップであって、前記回転体に、前記供給路とは別に、前記供給路の前記熱対流用流路との接続部に連通した封止剤用空間が形成され、前記封止剤用空間に常温で固形の封止剤が保持され、前記供給路により液体が供給された前記熱対流用流路を閉塞するために、前記封止剤用空間の前記封止剤を加温し、溶融させて、前記回転体を回転させたときの遠心力により、前記接続部に移送し充填可能にされている。A fourth aspect of the present invention is a thermal convection generating chip that includes a rotor having a thermal convection flow path, an inlet, and a supply path formed therein, and that supplies liquid introduced into the inlet to the thermal convection flow path through the supply path and causes thermal convection in the thermal convection flow path, wherein a sealant space is formed in the rotor, separate from the supply path, that is connected to the connection part of the supply path with the thermal convection flow path, and a sealant that is solid at room temperature is held in the sealant space, and in order to block the thermal convection flow path to which liquid is supplied through the supply path, the sealant in the sealant space is heated and melted, and is transported to the connection part by the centrifugal force generated when the rotor is rotated so that it can be filled.

本発明の第1の態様によれば、供給路への液体の導入が確実になり、供給不足を防げるから、熱対流用流路への液体供給量の精度を向上することができる。
本発明の第2の態様によれば、供給量を秤量する秤量空間から熱対流用流路側への液体の意図しない漏出が防がれるから、熱対流用流路への液体供給量の精度を向上することができる。
本発明の第3の態様によれば、余剰液が余剰液貯留部に保持されるから、熱対流用流路への液体供給量の精度を向上することができる。
本発明の第4の態様によれば、適切なタイミングでの加温と回転により、熱対流生成用チップ内に既設の封止剤で熱対流用流路を閉塞できるから、熱対流用流路への液体供給量の精度を維持することができる。
According to the first aspect of the present invention, the introduction of liquid into the supply passage is ensured and supply shortages can be prevented, so that the accuracy of the amount of liquid supplied to the thermal convection passage can be improved.
According to the second aspect of the present invention, unintended leakage of liquid from the measuring space for measuring the supply amount to the thermal convection flow path side is prevented, thereby improving the accuracy of the amount of liquid supplied to the thermal convection flow path.
According to the third aspect of the present invention, since the surplus liquid is stored in the surplus liquid storage section, it is possible to improve the accuracy of the amount of liquid supplied to the thermal convection flow path.
According to the fourth aspect of the present invention, by heating and rotating at an appropriate timing, the thermal convection flow path can be blocked with the sealant already installed in the thermal convection generating chip, thereby maintaining the accuracy of the amount of liquid supplied to the thermal convection flow path.

本発明の一実施形態に係る熱対流生成用チップの上面斜視図である。FIG. 2 is a top perspective view of a thermal convection generating chip according to an embodiment of the present invention. 本発明の一実施形態に係る熱対流生成用チップの上面斜視図であって、上蓋を外した状態を示す。FIG. 1 is a top perspective view of a thermal convection generating chip according to an embodiment of the present invention, showing a state in which a top cover is removed. 本発明の一実施形態に係る熱対流生成用チップの底面斜視図である。FIG. 2 is a bottom perspective view of a thermal convection generating chip according to an embodiment of the present invention. 本発明の一実施形態に係る熱対流生成用チップの底面斜視図であって、底蓋を外した状態を示す。FIG. 2 is a bottom perspective view of the thermal convection generating chip according to the embodiment of the present invention, showing a state in which the bottom cover is removed. 本発明の一実施形態に係る熱対流生成用チップの上面図であって、上蓋を外した状態を示す。FIG. 2 is a top view of the thermal convection generating chip according to the embodiment of the present invention, showing a state in which the top cover is removed. 本発明の一実施形態に係る熱対流生成用チップの底面図であって、底蓋を外した状態を示す。FIG. 2 is a bottom view of the thermal convection generating chip according to the embodiment of the present invention, showing a state in which the bottom cover is removed. 本発明の一実施形態に係る熱対流生成用チップの中央部縦断面図である。1 is a vertical cross-sectional view of a central portion of a thermal convection generating chip according to an embodiment of the present invention. 本発明の一実施形態に係る熱対流生成用チップの部分拡大上面斜視図であって、上蓋を外した状態を示す。FIG. 2 is a partially enlarged top perspective view of the thermal convection generating chip according to the embodiment of the present invention, showing a state in which the top cover is removed. 本発明の一実施形態に係る熱対流生成用チップの部分拡大上面斜視図であって、上蓋を外した状態を示す。図8とは異なる角度から見た斜視図である。8 is a partially enlarged top perspective view of the thermal convection generating chip according to the embodiment of the present invention, showing a state in which the top cover is removed. 本発明の一実施形態に係る熱対流生成用チップの部分拡大上面図であって、上蓋を外した状態を示す。FIG. 2 is a partially enlarged top view of the thermal convection generating chip according to the embodiment of the present invention, showing a state in which the top cover is removed. 本発明の一実施形態に係る熱対流生成用チップの部分拡大底面斜視図であって、底蓋を外した状態を示す。FIG. 2 is a partially enlarged bottom perspective view of the thermal convection generating chip according to the embodiment of the present invention, showing a state in which the bottom cover is removed.

以下に本発明の一実施形態につき図1から図11を参照して説明する。以下は本発明の一実施形態であって本発明を限定するものではない。One embodiment of the present invention will be described below with reference to Figures 1 to 11. The following is one embodiment of the present invention and is not intended to limit the present invention.

図1等に示すように本実施形態の熱対流生成用チップ1は、ディスク状マイクロ流路チップであり、ディスク1aと上部円筒1bとを同軸Aで連接した構造の回転体1cを本体とする。
ディスク1aは、コア基板2と、上部円筒1bを挿入できるリング状の上蓋3と、底蓋4と備える。コア基板2は、上面2Aと下面2Bとを有する。コア基板2に流路等を構成する溝が形成され、その溝の上面開口が上蓋3で閉じられ、下面開口が底蓋4で閉じられることで流路と空気路が形成される。但し、上面に設けられた空気口100は、開放されている。
ディスク1aの外縁部には、回転時等に保持される切り欠き99が形成されている。
As shown in FIG. 1 etc., the thermal convection generating chip 1 of this embodiment is a disk-shaped microchannel chip, and its main body is a rotor 1c having a structure in which a disk 1a and an upper cylinder 1b are connected by a coaxial line A.
The disk 1a comprises a core substrate 2, a ring-shaped top cover 3 into which the upper cylinder 1b can be inserted, and a bottom cover 4. The core substrate 2 has an upper surface 2A and a lower surface 2B. A groove constituting a flow path etc. is formed in the core substrate 2, and the upper opening of the groove is closed by the top cover 3 and the lower opening is closed by the bottom cover 4 to form a flow path and an air passage. However, an air vent 100 provided on the top surface is left open.
The outer edge of the disk 1a is formed with a notch 99 for supporting the disk during rotation, etc.

また、熱対流生成用チップ1は、12チャンネルのPCR用のマイクロ流路チップであり、ディスク1aに、12組の熱対流用流路5と、これに溶液を供給する供給路10が中心角を12等分して分割した範囲に配設されている。熱対流用流路5は、円環状に形成された流路である。
上部円筒1bの上端開口は導入口50である。導入口50の下の空間は、導入口50に連通する液体受容部51である。液体受容部51の底面は、底蓋4の上面により構成されている。
導入口50に導入された液体を、12の供給路10により12の熱対流用流路5に分配供給し、各熱対流用流路5で熱対流させる。
The thermal convection generating chip 1 is a 12-channel microchannel chip for PCR, and 12 sets of thermal convection channels 5 and supply channels 10 for supplying solutions thereto are arranged on the disk 1a in an area divided by 12 equal central angles. The thermal convection channels 5 are channels formed in an annular shape.
The upper end opening of the upper cylinder 1b is an inlet 50. The space below the inlet 50 is a liquid receiving portion 51 that communicates with the inlet 50. The bottom surface of the liquid receiving portion 51 is formed by the upper surface of the bottom cover 4.
The liquid introduced into the inlet 50 is distributed and supplied to the twelve thermal convection flow paths 5 by the twelve supply paths 10, and thermal convection is caused in each of the thermal convection flow paths 5.

供給路10の構成を、最上流の液体受容部51から最下流の熱対流用流路5までの順番で挙げると次の通りである。
すなわち、供給路10は、上流端が液体受容部51に接続した第1通路11、次に第2通路12、さらに秤量空間13、最後に導入室14と連なった構成であり、導入室14の下流端が熱対流用流路5に接続する。
液体受容部51、第1通路11、第2通路12、秤量空間13、導入室14、熱対流用流路5の順で直列に連続している。
第1通路11、第2通路12及び秤量空間13は、液体受容部51内の液体を毛細管現象により吸引する吸引通路に相当する。したがって、液体受容部51内の液体は、毛細管現象により第1通路11、第2通路12と通って、秤量空間13に充填される。
第1通路11は、径方向外方に遷移する流路である。第2通路12は、径方向内方に遷移する流路である。秤量空間13は、径方向外方に遷移する流路である。なお、「径方向」というときは、回転体1cの回転中心軸Aを中心とした径方向を指す。
さらに、秤量空間13より径方向外方に導入室14が配置される。導入室14より径方向外方に熱対流用流路5が配置される。
The configuration of the supply path 10, from the most upstream liquid receiving portion 51 to the most downstream thermal convection path 5, is as follows.
That is, the supply path 10 is configured to be connected to a first passage 11 whose upstream end is connected to the liquid receiving portion 51, then to a second passage 12, then to a weighing space 13, and finally to an introduction chamber 14, the downstream end of which is connected to the thermal convection flow path 5.
The liquid receiving portion 51, the first passage 11, the second passage 12, the weighing space 13, the introduction chamber 14, and the thermal convection flow path 5 are connected in series in this order.
The first passage 11, the second passage 12, and the measuring space 13 correspond to a suction passage that draws in the liquid in the liquid receiving portion 51 by capillary action. Therefore, the liquid in the liquid receiving portion 51 passes through the first passage 11 and the second passage 12 by capillary action and fills the measuring space 13.
The first passage 11 is a flow path that transitions radially outward. The second passage 12 is a flow path that transitions radially inward. The weighing space 13 is a flow path that transitions radially outward. Note that the term "radial direction" refers to the radial direction centered on the rotation central axis A of the rotor 1c.
Furthermore, an introduction chamber 14 is disposed radially outward from the weighing space 13. A thermal convection flow path 5 is disposed radially outward from the introduction chamber 14.

秤量空間13の上流端部の上面に空気導入口13aが開口している。秤量空間13の下流端部の上面に出口13bが開口している。
回転体1cの静止状態においては、毛細管現象により秤量空間13を満たす液体は、空気導入口13a及び出口13bに表面を張る形で止まる。
An air inlet 13a opens at an upper surface of the upstream end of the weighing space 13. An air outlet 13b opens at an upper surface of the downstream end of the weighing space 13.
When the rotor 1c is in a stationary state, the liquid filling the measuring space 13 due to capillary action stays on the surfaces of the air inlet 13a and the outlet 13b.

次に、液体受容部51から熱対流用流路5までの直列系統以外の流路、空間について説明する。
第1通路11の下流端及び第2通路12の上流端は、余剰液貯留部15の上流端に接続している。
余剰液貯留部15の上流端部には、ダム部15aが形成されている。
余剰液貯留部15は、熱対流用流路5の径方向外側を迂回して、自身の径方向最外端15eを跨るように円弧状に延在している。余剰液貯留部15の下流端部は、径方向最外端15eより径方向内方で、空気路16aに接続する。空気路16a、フィルター設置室17、空気路18の順で連続する。
導入室14には、封止剤供給路19を介して封止剤用空間20が連通する。封止剤用空間20は、遠心力での封止剤の供給を可能にするため、導入室14より径方向内方に配置されている。
また、秤量空間13の空気導入口13a及び封止剤用空間20の径方向内端は、空気路16bに接続する。空気路16b、フィルター設置室17、空気路18の順で連続する。
空気路18の上蓋3で塞がれない部分が空気口100である。空気口100からの液体漏洩を防ぐため、空気口100は秤量空間13及び封止剤用空間20から径方向内方に離れた位置に設置されている。フィルター設置室17には、空気を通し、液体を通さない性質のフィルターが設置される。
Next, the flow paths and spaces other than the serial system from the liquid receiving portion 51 to the thermal convection flow path 5 will be described.
The downstream end of the first passage 11 and the upstream end of the second passage 12 are connected to the upstream end of the surplus liquid storage portion 15 .
A dam portion 15 a is formed at the upstream end of the surplus liquid storage portion 15 .
The surplus liquid storage section 15 extends in an arc shape so as to bypass the radially outer side of the thermal convection flow path 5 and straddle its own radially outermost end 15e. The downstream end of the surplus liquid storage section 15 connects to the air passage 16a radially inward from the radially outermost end 15e. The air passage 16a, the filter installation chamber 17, and the air passage 18 are connected in this order.
The introduction chamber 14 communicates with a sealant space 20 via a sealant supply path 19. The sealant space 20 is disposed radially inward from the introduction chamber 14 so as to enable the supply of the sealant by centrifugal force.
The air inlet 13a of the weighing space 13 and the radially inner end of the sealant space 20 are connected to the air passage 16b. The air passage 16b, the filter installation chamber 17, and the air passage 18 are connected in this order.
The portion of the air passage 18 that is not blocked by the upper cover 3 is the air port 100. To prevent liquid leakage from the air port 100, the air port 100 is provided at a position radially inward and away from the weighing space 13 and the sealant space 20. A filter that allows air to pass through but does not allow liquid to pass through is provided in the filter installation chamber 17.

以上の構成により、回転体1cを回転させたときの遠心力により、秤量空間13内の液体が他の領域(11、12)内の液体から分離して熱対流用流路5に供給される。このとき、空気路16bからの空気導入により、秤量空間13内の液体と第2通路12内の液体との分離が促進される。With the above configuration, the liquid in the weighing space 13 is separated from the liquid in the other regions (11, 12) by the centrifugal force generated when the rotor 1c is rotated and is supplied to the thermal convection flow path 5. At this time, the introduction of air from the air path 16b promotes the separation of the liquid in the weighing space 13 from the liquid in the second passage 12.

図7に示すように液体受容部51の内側面51aと内底面51bとが鋭角を成して接している。
供給路10は、液体受容部51の内底面51b上に底辺を配置して内側面51aに開口した液体流入口11aを有する。内底面51bは、底蓋4の上面で構成されている。液体流入口11aは、第1通路11の上流端開口である。第1通路11の内底面も底蓋4の上面で構成されているから、液体受容部51の内底面51bと、第1通路11の内底面とは同じ高さレベルである。したがって、液体流入口11aの底辺は液体受容部51の内底面51b上に配置されている。
以上のように、液体流入口11aが開口する面(内側面51a)が、液体受容部51の内底面51bに対して鋭角に接して連続し、液体流入口11aの手前に、隣り合う面が鋭角をつくる狭小空間を形成することで、そこに毛細管現象を生じさせ、液体受容部51内の液体を素早く液体流入口11aに流入させることができる。
これにより供給路10への液体の導入が迅速、確実になり、供給不足を防げるから、熱対流用流路5への液体供給量の精度を向上することができる。
As shown in FIG. 7, the inner side surface 51a and the inner bottom surface 51b of the liquid receiving portion 51 meet at an acute angle.
The supply path 10 has a liquid inlet 11a that opens to the inner side surface 51a and has its bottom side located on the inner bottom surface 51b of the liquid receiving portion 51. The inner bottom surface 51b is formed by the upper surface of the bottom lid 4. The liquid inlet 11a is the upstream end opening of the first passage 11. Since the inner bottom surface of the first passage 11 is also formed by the upper surface of the bottom lid 4, the inner bottom surface 51b of the liquid receiving portion 51 and the inner bottom surface of the first passage 11 are at the same height level. Therefore, the bottom side of the liquid inlet 11a is located on the inner bottom surface 51b of the liquid receiving portion 51.
As described above, the surface (inner surface 51a) through which the liquid inlet 11a opens is continuous with the inner bottom surface 51b of the liquid receiving section 51 at an acute angle, and a narrow space is formed in front of the liquid inlet 11a where the adjacent surfaces form an acute angle, thereby generating capillary action there and allowing the liquid in the liquid receiving section 51 to quickly flow into the liquid inlet 11a.
This allows the liquid to be introduced into the supply passage 10 quickly and reliably, preventing a supply shortage, and improving the accuracy of the amount of liquid supplied to the thermal convection passage 5 .

本実施形態にあっては、複数組の供給路10の液体流入口11aが、一つの液体受容部51の内側面51aに同様に開口して設けられている。これにより、一つの液体受容部51から溶液を分配することが可能である。
また、導入口50及び液体受容部51の中心軸Aが回転体1cの回転中心軸A上に配置され、液体受容部51の内側面51aは、回転中心軸Aから等距離に配置されている。さらに、液体受容部51の内側面51aの少なくとも下部は、低位置ほど広がるテーパー面で形成され、当該テーパー面に液体流入口11aが開口している。これにより、液体を一つの液体受容部51から複数組の供給路10に均等かつ同時に分配することが容易である。
In this embodiment, the liquid inlets 11a of the multiple sets of supply paths 10 are similarly provided to open on the inner surface 51a of one liquid receiving portion 51. This makes it possible to distribute the solution from one liquid receiving portion 51.
The central axis A of the inlet 50 and the liquid receiving portion 51 is disposed on the central axis A of rotation of the rotor 1c, and the inner side surface 51a of the liquid receiving portion 51 is disposed equidistant from the central axis A of rotation. Furthermore, at least the lower portion of the inner side surface 51a of the liquid receiving portion 51 is formed as a tapered surface that widens as it lowers, and the liquid inlet 11a opens into the tapered surface. This makes it easy to distribute liquid from one liquid receiving portion 51 to multiple sets of supply paths 10 evenly and simultaneously.

図10に示すように秤量空間13の熱対流用流路5側の出口13bは、当該出口13bの縁を回転体1cが形成する平面13dの縁から離間して当該平面13dに開口している。これにより、出口13bを取り囲む周囲の面は、当該出口13bの開口面を含む平面上に配置される。そのため、出口13bまで到達した液体が、出口13bの外側の面に接触することが防がれ、出口13bから液体が漏れ出すことが防がれる。仮に出口13bから漏れ出した液体がある場合、同液体は熱対流用流路5に導入されてしまうから、秤量精度が落ちる。したがって、出口13bから液体が漏れ出すことが防がれることで、秤量精度が向上する。
秤量空間13の空気導入口13aも、同様に当該空気導入口13aの縁を回転体1cが形成する平面13cの縁から離間して当該平面13cに開口している。
したがって、空気導入口13aから液体が漏れ出すことも防がれ、秤量精度が向上する。
以上のようにして、秤量空間13を満たす容量の液体のみが熱対流用流路5に供給されるので、熱対流用流路5への液体供給量の精度を向上することができる。
なお、本実施形態においては、出口13bが開口する平面13d及び空気導入口13aが開口する平面13cは、いずれも上向きの水平面とされているが、上記の液体の漏れ出しを防ぐ効果を得るためには、出口13bや空気導入口13aの開口面の角度は、どのような角度でもよい。例えば、出口13bや空気導入口13aを垂直面や下向きの水平面に開口するようにしても同様の効果が得られる。
As shown in Fig. 10, the outlet 13b on the thermal convection flow path 5 side of the weighing space 13 is opened on the plane 13d formed by the rotor 1c with the edge of the outlet 13b separated from the edge of the plane 13d. As a result, the surface surrounding the outlet 13b is arranged on a plane including the opening surface of the outlet 13b. Therefore, the liquid that has reached the outlet 13b is prevented from contacting the outer surface of the outlet 13b, and the liquid is prevented from leaking out of the outlet 13b. If there is any liquid leaking out of the outlet 13b, the liquid will be introduced into the thermal convection flow path 5, and the weighing accuracy will decrease. Therefore, by preventing the liquid from leaking out of the outlet 13b, the weighing accuracy will be improved.
Similarly, the edge of the air inlet 13a of the weighing space 13 is spaced apart from the edge of a plane 13c formed by the rotor 1c and opens onto the plane 13c.
This prevents liquid from leaking out of the air inlet 13a, improving weighing accuracy.
In this manner, only the volume of liquid that fills the weighing space 13 is supplied to the thermal convection channel 5, so that the accuracy of the amount of liquid supplied to the thermal convection channel 5 can be improved.
In this embodiment, the plane 13d where the outlet 13b opens and the plane 13c where the air inlet 13a opens are both horizontal planes facing upward, but in order to obtain the effect of preventing the leakage of the liquid, the opening planes of the outlet 13b and the air inlet 13a may have any angle. For example, the same effect can be obtained even if the outlet 13b and the air inlet 13a are opened on a vertical plane or a horizontal plane facing downward.

余剰液貯留部15は、回転体1cの回転による遠心力により秤量空間13内の液体から分離した液体(通路11,12内の液体)が貯留される空間である。空気路16aを介した排気により、余剰液貯留部15への液体の流入が促進される。余剰液貯留部15は、熱対流用流路5と径方向同位置から外側に及んでいるので、回転体1cの回転による遠心力が、熱対流用流路5と同等以上に作用する。回転体1cの回転による遠心力が働いているとき、余剰液貯留部15の径方向最外端15eを中心に液体が保持されやすくされており、余剰液貯留部15の下流端部の空気路16bまでには液体が移動し難くされている。The surplus liquid storage section 15 is a space in which liquid (liquid in passages 11 and 12) separated from the liquid in the weighing space 13 by the centrifugal force caused by the rotation of the rotor 1c is stored. Exhaust through the air passage 16a promotes the inflow of liquid into the surplus liquid storage section 15. Since the surplus liquid storage section 15 extends outward from the same radial position as the thermal convection flow path 5, the centrifugal force caused by the rotation of the rotor 1c acts on the surplus liquid storage section 15 to the same extent or greater than that of the thermal convection flow path 5. When the centrifugal force caused by the rotation of the rotor 1c is acting, liquid is easily retained around the radially outermost end 15e of the surplus liquid storage section 15, and liquid is difficult to move to the air passage 16b at the downstream end of the surplus liquid storage section 15.

ダム部15aは、余剰液貯留部の底面から上に突出し両側側面間を横断するように形成されている。ダム部15aは、余剰液貯留部15から流出しようとする液体を堰き止める作用がある。ダム部15aは、径方向最外端15eより径方向内方に設けられる。ダム部15aを2重以上に設けてもよい。
余剰液貯留部15の流路断面は、丸みがつけられた角部15Rを有する。丸みがつけられた角部15Rは、ダム部15aにおいては、ダム部15aと両側側面とでつくる角部である。それ以外では、余剰液貯留部15の天面と両側側面とでつくる角部は丸みがつけられた角部15Rである。上蓋3又は底蓋4と、コア基板2とでつくる角部は、成形の都合上、丸みをつけることができないためである。
シャープな角部は毛細管現象を生じさせる。角部15Rに丸みがつけられていることで、毛細管現象による逆流を抑えることができる。そのため、余剰液貯留部15に一旦流入した余剰液が、再び第1通路11や第2通路12の方へ逆流することが防がれる。また、余剰液貯留部15は毛細管現象による流動が抑えられているので、回転体1cの静止状態において液体受容部51の液体が毛細管現象により第1通路11、第2通路12を通って秤量空間13に導入される際、余剰液貯留部15への当該液体の流入も抑えられる。そのため、12チャンネルあるうちの一部の余剰液貯留部15に液体が偏って多く流入することにより、12チャンネルに対し不均等に液体が分配される事態を防ぐ効果がある。
ダム部15aが設けられることにより、天面側のみならず底面側にも丸みをつけた角部15Rを設けることができるので、角部に沿って逆流しようとする液体は、丸みがつけられたいずれかの角部15Rに阻まれる。角部15Rの曲率半径は0.1mm以上が好ましい。
以上により、余剰液が余剰液貯留部15に確実に保持されるから、熱対流用流路5への液体供給量の精度を向上することができる。
The dam portion 15a is formed so as to protrude upward from the bottom surface of the excess liquid storage portion and cross between both side surfaces. The dam portion 15a has the effect of blocking liquid attempting to flow out of the excess liquid storage portion 15. The dam portion 15a is provided radially inward from the radially outermost end 15e. Two or more dam portions 15a may be provided.
The flow path cross section of the surplus liquid storage section 15 has rounded corners 15R. In the dam section 15a, the rounded corners 15R are corners formed by the dam section 15a and both side surfaces. In other cases, corners formed by the top surface and both side surfaces of the surplus liquid storage section 15 are rounded corners 15R. This is because corners formed by the top cover 3 or bottom cover 4 and the core substrate 2 cannot be rounded for molding reasons.
Sharp corners cause capillary action. The rounded corners 15R can suppress backflow due to capillary action. Therefore, the excess liquid that has once flowed into the excess liquid storage section 15 is prevented from flowing back toward the first passage 11 or the second passage 12. In addition, since the flow due to capillary action is suppressed in the excess liquid storage section 15, when the liquid in the liquid receiving section 51 is introduced into the weighing space 13 through the first passage 11 and the second passage 12 by capillary action while the rotor 1c is in a stationary state, the flow of the liquid into the excess liquid storage section 15 is also suppressed. Therefore, it is effective in preventing a situation in which the liquid flows unevenly into some of the excess liquid storage sections 15 out of the 12 channels, resulting in uneven distribution of the liquid among the 12 channels.
By providing the dam portion 15a, it is possible to provide rounded corners 15R not only on the top surface side but also on the bottom surface side, so that liquid that attempts to flow back along the corners is blocked by one of the rounded corners 15R. The radius of curvature of the corners 15R is preferably 0.1 mm or more.
As a result, the surplus liquid is reliably stored in the surplus liquid storage section 15, so that the accuracy of the amount of liquid supplied to the thermal convection flow path 5 can be improved.

流路断面の角部(15R)の曲率半径と、当該角部を辿った流動距離との関係を調べた実験内容を以下に開示する。
樹脂板の上面に深さ0.5mm、幅2.5mm、長さ30.0mmの溝を必要本数形成し、この溝を実験用の流路とした。したがって、実験用の流路は、底面と一方の側面とでつくる角部、底面と他方の側面とでつくる角部があり、上面は開放されている。
実験用の流路として、その2つの角部の曲率半径Rを、0.0、0.05、0.1、0.2、0.3とした5種を用意した。
樹脂板を水平に保ち、各実験用の流路の長手方向の端部に色付き溶液を同量(5μリットル)注入し、観察した。すると、色付き溶液が、流路の両側角部に沿って延びるように移動した。注入から90秒後の移動距離は以下の通りとなった。
R=0.0の流路では、22.3mm
R=0.05の流路では、14.1mm
R=0.1の流路では、7.0mm
R=0.2の流路では、3.2mm
R=0.3の流路では、2.8mm
The details of an experiment conducted to investigate the relationship between the radius of curvature of the corner (15R) of the flow passage cross section and the flow distance that follows the corner will be disclosed below.
A required number of grooves, each 0.5 mm deep, 2.5 mm wide, and 30.0 mm long, were formed on the top surface of the resin plate, and these grooves were used as flow paths for the experiment. Therefore, the flow path for the experiment had a corner formed by the bottom surface and one side surface, and a corner formed by the bottom surface and the other side surface, and the top surface was open.
Five types of flow paths were prepared for the experiment, with the radii of curvature R of the two corners being 0.0, 0.05, 0.1, 0.2, and 0.3.
The resin plate was held horizontally, and the same amount (5 μL) of colored solution was injected into the longitudinal end of each experimental flow channel, and the flow channel was observed. The colored solution then migrated along both corners of the flow channel. The migration distances 90 seconds after injection were as follows:
For a flow path of R=0.0, it is 22.3 mm.
For a flow path with R=0.05, it is 14.1 mm.
For a flow path of R=0.1, it is 7.0 mm.
For a flow path of R=0.2, it is 3.2 mm.
For a flow path of R=0.3, it is 2.8 mm.

また、ダム部15a及びその前部15b、後部15cは、後部15cよりさらに流入方向下流の貯留部15dに対して流路幅が拡幅している。これにより、角部を辿った逆流経路は長くなるから、さらに余剰液貯留部15内の液体が逆流して第1通路11や第2通路12の方へ流出することは難しくなる。
なお、前部15b及び後部15cの流路断面には、コア基板2を上下に貫通するので、丸みをつけた角部15Rは設けられていない。しかし、前部15b及び後部15c内の縦方向の角部15Uは丸みがつけられている。角部15Uの曲率半径の軸が回転体1cの回転中心軸Aに平行である。丸みがつけられた角部15Rに加え、丸みがつけられた角部15Uがあることによって、さらに余剰液貯留部15における毛細管現象による流動が抑えられており、意図しない流入や逆流が防がれる。
ダム部15a及び貯留部15dには丸みをつけた角部15Rが設けられている。
In addition, the dam portion 15a and its front portion 15b and rear portion 15c have a flow path width wider than the reservoir portion 15d which is further downstream in the inflow direction than the rear portion 15c. This lengthens the backflow path that follows the corner, making it more difficult for the liquid in the surplus liquid reservoir portion 15 to flow back and flow out toward the first passage 11 or the second passage 12.
In addition, the flow path cross sections of the front portion 15b and the rear portion 15c do not have rounded corners 15R because they vertically penetrate the core substrate 2. However, the vertical corners 15U in the front portion 15b and the rear portion 15c are rounded. The axis of the radius of curvature of the corners 15U is parallel to the central axis A of the rotation body 1c. In addition to the rounded corners 15R, the presence of the rounded corners 15U further suppresses the flow due to capillary action in the excess liquid storage portion 15, preventing unintended inflow and backflow.
The dam portion 15a and the storage portion 15d are provided with rounded corners 15R.

上述したように、回転体1cに、供給路10とは別に、供給路10の熱対流用流路5との接続部、すなわち、導入室14に連通した封止剤用空間20が形成されている。
封止剤用空間20に常温で固形の封止剤としてパラフィン等が予め装填され、その後に上蓋3及び底蓋4がコア基板2に付けられる。
上述したように、毛細管現象による秤量空間13への液体導入と、その後の回転体1cの回転により、熱対流用流路5に液体受容部51からの液体が導入された後、次のようにして熱対流用流路5を閉塞する。
すなわち、封止剤用空間20の封止剤を加温し、溶融させて、回転体1cを回転させたときの遠心力により、接続部(導入室14)に移送し充填する。このとき、空気路16bからの空気導入により、封止剤用空間20からの封止剤の流出が促進される。
これにより、導入室14が封止剤で満たされ、熱対流用流路5が閉塞される。したがって、導入室14は、秤量空間13より下流で熱対流用流路5に隣接し、封止剤の充填により熱対流用流路5の入口を閉じるための空間でもある。熱対流用流路5が閉塞されるため、熱対流用流路5内の液体の蒸発等による漏出が防がれる。
以上のように、適切なタイミングでの加温と回転により、熱対流生成用チップ1内に既設の封止剤で熱対流用流路5を閉塞できるから、熱対流用流路5への液体供給量の精度を維持することができる。
As described above, in addition to the supply path 10, the rotary body 1c is formed with a connection portion of the supply path 10 with the thermal convection flow path 5, i.e., the sealant space 20 communicating with the introduction chamber 14.
The sealant space 20 is filled in advance with paraffin or the like as a sealant that is solid at room temperature, and then the top cover 3 and the bottom cover 4 are attached to the core substrate 2 .
As described above, after the liquid is introduced into the weighing space 13 by capillary action and the liquid is then introduced into the thermal convection flow path 5 from the liquid receiving portion 51 by the rotation of the rotating body 1c, the thermal convection flow path 5 is blocked as follows.
That is, the sealant in the sealant space 20 is heated and melted, and is transferred and filled into the connection part (introduction chamber 14) by the centrifugal force generated when the rotor 1c is rotated. At this time, the outflow of the sealant from the sealant space 20 is promoted by the introduction of air from the air passage 16b.
As a result, the introduction chamber 14 is filled with the sealant, and the thermal convection path 5 is blocked. Therefore, the introduction chamber 14 is adjacent to the thermal convection path 5 downstream of the weighing space 13, and also serves as a space for closing the inlet of the thermal convection path 5 by filling with the sealant. Since the thermal convection path 5 is blocked, leakage due to evaporation of the liquid in the thermal convection path 5, etc., is prevented.
As described above, by heating and rotating at the appropriate timing, the thermal convection flow path 5 can be blocked with the sealant already installed in the thermal convection generating chip 1, thereby maintaining the accuracy of the amount of liquid supplied to the thermal convection flow path 5.

改めて、液体導入から熱対流反応までの手順を説明すると次の通りである。
予め、各熱対流用流路5には、プライマーDNAやプローブDNAが乾燥した状態で配置されている。これにより多種のDNA(菌種)に対応する。
まず、所定の反応試薬溶液を収容した検体容器に、採取した生体物質である検体を混入して、検体及び反応試薬を含有した溶液とする。同検体容器としては、下端開口がアルミ箔等でラミネートされているものを用いる。
液体受容部51の中央には、上に尖った開封用突起52が設けられている。
同検体容器を導入口50から液体受容部51に挿入し、開封用突起52によりラミネートを破って同検体容器を開封して、同検体容器内の検体及び反応試薬を含有した溶液を、液体受容部51に導入する。
The procedure from liquid introduction to the thermal convection reaction will be explained below.
Dried primer DNA and probe DNA are placed in advance in each thermal convection flow path 5. This allows for handling of many types of DNA (bacterial species).
First, a sample, which is a biological material collected, is mixed into a sample container containing a predetermined reaction reagent solution to produce a solution containing the sample and the reaction reagent. The sample container has a bottom opening laminated with aluminum foil or the like.
An upwardly pointed opening protrusion 52 is provided in the center of the liquid receiving portion 51 .
The specimen container is inserted into the liquid receiving section 51 through the inlet 50, the laminate is broken using the opening protrusion 52 to open the specimen container, and the solution containing the specimen and reaction reagent inside the specimen container is introduced into the liquid receiving section 51.

すると、上述したように秤量空間13までは溶液の自重と毛細管現象により同溶液が導入される。
秤量空間13が同溶液で満たされた後、回転体1cを回転させて、秤量空間13内の溶液のみ熱対流用流路5に供給する。
各組の供給路10及び熱対流用流路5で同様の流動が起こるので、溶液を複数組の熱対流用流路5に分配供給したことになる。
次に、上述した封止剤による熱対流用流路5の閉塞を行った後、当該各熱対流用流路5で溶液を各所定条件で熱対流させてポリメラーゼ連鎖反応又は逆転写ポリメラーゼ連鎖反応を行う。
Then, as described above, the solution is introduced into the weighing space 13 due to its own weight and capillary action.
After the weighing space 13 is filled with the solution, the rotor 1 c is rotated to supply only the solution in the weighing space 13 to the thermal convection flow path 5 .
Since a similar flow occurs in each set of supply paths 10 and thermal convection channels 5 , the solution is distributed and supplied to a plurality of sets of thermal convection channels 5 .
Next, after blocking the thermal convection channels 5 with the above-mentioned sealant, the solution is thermally convected in each of the thermal convection channels 5 under predetermined conditions to carry out a polymerase chain reaction or a reverse transcription polymerase chain reaction.

以上説明したように本実施形態の熱対流生成用チップによれば、熱対流用流路5への液体供給量の精度を向上することができる。
さらに、導入口50への検体容器の装填から熱対流反応までの作業を自動化することが容易であり、複数の熱対流用流路5での反応を同時に実施できるから、作業性を向上することができる。なお、導入口50への検体容器の装填は人手作業で実施してもよいが、機械に行わせることで、より安定した作業動作の制御と、より広範囲の自動化を実現することができる。特に、熱対流生成用チップ1には固形の封止剤が既設であり、検体容器の装填部が一か所(導入口50)であり、導入口50へ検体容器を装填した後は、回転体1cの回転と各部の温度の制御で実施可能であるので、作業性が向上し、自動化した場合による機械の作業負担も少なく自動化が容易である。
以上の実施形態の熱対流生成用チップでは、チャンネル数(熱対流用流路の数)を12チャンネルとしたが、チャンネル数に制限はなく、12チャンネルより多くする、12チャンネルより少なくするなど任意にチャンネル数を選択して実施し得る。これにより、必要チャンネル数に幅広く対応することが可能である。
As described above, according to the thermal convection generating chip of this embodiment, the accuracy of the amount of liquid supplied to the thermal convection channel 5 can be improved.
Furthermore, the work from loading the specimen container into the inlet 50 to the thermal convection reaction can be easily automated, and the reactions can be performed simultaneously in a plurality of thermal convection channels 5, improving workability. Although the loading of the specimen container into the inlet 50 may be performed manually, more stable control of the work operation and a wider range of automation can be realized by having a machine do it. In particular, the thermal convection generating chip 1 is already provided with a solid sealant, there is only one loading part for the specimen container (the inlet 50), and after loading the specimen container into the inlet 50, the work can be performed by controlling the rotation of the rotor 1c and the temperature of each part, improving workability and automating the work with less work load on the machine.
In the thermal convection generating chip of the above embodiment, the number of channels (the number of thermal convection flow paths) is 12, but there is no limit to the number of channels, and the number of channels can be arbitrarily selected to be more than 12 channels or less than 12 channels. This makes it possible to widely accommodate the number of channels required.

本発明は、熱対流生成用チップ及び反応方法に利用することができる。 The present invention can be used in chips for generating thermal convection and reaction methods.

1 熱対流生成用チップ
1a ディスク
1b 上部円筒
1c 回転体
2 コア基板
2A コア基板の上面
2B コア基板の下面
3 上蓋
4 底蓋
5 熱対流用流路
10 供給路
11 第1通路
11a 液体流入口
12 第2通路
13 秤量空間
13a 空気導入口
13b 出口
13c 平面
13d 平面
14 導入室
15 余剰液貯留部
15R 角部
15a ダム部
15b ダム部の前部
15c ダム部の後部
15d 貯留部
15e 余剰液貯留部の径方向最外端
16a 空気路
16b 空気路
17 フィルター設置室
18 空気路
19 封止剤供給路
20 封止剤用空間
50 導入口
51 液体受容部
51a 内側面
51b 内底面
52 開封用突起
99 切り欠き
100 空気口
A 回転中心軸
1 Thermal convection generating chip 1a Disk 1b Upper cylinder 1c Rotating body 2 Core substrate 2A Upper surface 2B of core substrate Lower surface 3 Upper lid 4 Bottom lid 5 Thermal convection flow path 10 Supply path 11 First passage 11a Liquid inlet 12 Second passage 13 Weighing space 13a Air inlet 13b Outlet 13c Plane 13d Plane 14 Introduction chamber 15 Excess liquid storage section 15R Corner 15a Dam section 15b Front part 15c Rear part 15d of dam section Storage section 15e Radially outermost end 16a of excess liquid storage section Air path 16b Air path 17 Filter installation chamber 18 Air path 19 Sealant supply path 20 Sealant space 50 Introduction port 51 Liquid receiving section 51a Inner surface 51b Inner bottom surface 52 Opening protrusion 99 Notch 100 Air vent A Rotational axis

Claims (10)

入口が形成されるとともに、供給路と熱対流用流路との組複数組形成された回転体を備え、前記導入口に導入された液体を前記供給路それぞれにより、対応する前記熱対流用流路に供給し、複数の前記熱対流用流路で熱対流させる熱対流生成用チップであって、
前記回転体に、前記導入口に連通する円筒状の液体受容部が形成され、
前記液体受容部の内側面と内底面とが鋭角を成して接し、
複数の前記供給路の各々は、前記液体受容部の前記内底面上に底辺を配置して前記内側面に開口した液体流入口を有する熱対流生成用チップ。
A thermal convection generating chip comprising a rotor in which an inlet is formed and in which a plurality of pairs of supply paths and thermal convection flow paths are formed, the thermal convection generating chip supplies liquid introduced into the inlet to a corresponding one of the thermal convection flow paths through each of the supply paths, and thermally convects the liquid in the plurality of thermal convection flow paths,
The rotor is provided with a cylindrical liquid receiving portion that is in communication with the inlet,
The inner surface and the inner bottom surface of the liquid receiving portion meet at an acute angle,
Each of the plurality of supply paths is a thermal convection generating chip having a liquid inlet opening on the inner side surface, with the bottom side being disposed on the inner bottom surface of the liquid receiving portion.
前記導入口及び前記液体受容部の中心軸が前記回転体の回転中心軸上に配置され、
前記液体受容部の内側面は、前記回転中心軸から等距離に配置され、
前記液体受容部の内側面の少なくとも下部は、低位置ほど広がるテーパー面で形成され、
前記テーパー面に前記供給路それぞれの前記液体流入口が開口している請求項に記載の熱対流生成用チップ。
the central axes of the inlet and the liquid receiving portion are disposed on the central axis of rotation of the rotor,
The inner surface of the liquid receiving portion is disposed equidistant from the central axis of rotation,
At least a lower portion of the inner surface of the liquid receiving portion is formed as a tapered surface that widens toward a lower position,
2. The thermal convection generating chip according to claim 1 , wherein the liquid inlet of each of the supply paths opens onto the tapered surface.
入口が形成されるとともに、供給路と熱対流用流路との組複数組形成された回転体を備え、前記導入口に導入された液体を前記供給路それぞれにより、対応する前記熱対流用流路に供給し、複数の前記熱対流用流路で熱対流させる熱対流生成用チップであって、
前記回転体に、前記導入口に連通する円筒状の液体受容部が形成され、
複数の前記供給路の各々は、前記液体受容部内の液体を毛細管現象により吸引する吸引通路を有し、
前記吸引通路は、秤量空間を有し、
前記吸引通路は、前記回転体を回転させたときの遠心力により、前記秤量空間内の液体が他の領域内の液体から分離して、対応する前記熱対流用流路に供給されよう構成され、
前記回転体は、複数の前記供給路と複数の前記熱対流用流路とが形成された基板を有し、
前記基板は、前記秤量空間のそれぞれの前記熱対流用流路側の出口に連通する開口を有し、
前記秤量空間のそれぞれ前記口のは、対応する前記基板の前記開口の縁からそれぞれ離間して開口している熱対流生成用チップ。
A thermal convection generating chip comprising a rotor in which an inlet is formed and in which a plurality of pairs of supply paths and thermal convection flow paths are formed, the thermal convection generating chip supplies liquid introduced into the inlet to a corresponding one of the thermal convection flow paths through each of the supply paths, and thermally convects the liquid in the plurality of thermal convection flow paths,
The rotor is provided with a cylindrical liquid receiving portion that is in communication with the inlet,
Each of the plurality of supply paths has a suction passage that draws in the liquid in the liquid receiving portion by capillary action,
The suction passage has a weighing space,
the suction passage is configured so that the liquid in the measuring space is separated from the liquid in other regions by centrifugal force generated when the rotor is rotated , and the liquid is supplied to the corresponding thermal convection passage;
the rotating body has a substrate on which a plurality of the supply paths and a plurality of the thermal convection paths are formed,
the substrate has an opening communicating with an outlet of each of the weighing spaces on the thermal convection flow path side,
a thermal convection generating chip in which an edge of each of the outlets of the weighing spaces is open and spaced apart from an edge of the opening of the corresponding substrate ;
前記秤量空間のそれぞれの前記出口は、対応する前記基板の前記開口にそれぞれ対向する、請求項3に記載の熱対流生成用チップ。The thermal convection generating chip according to claim 3 , wherein the outlets of the weighing spaces face the corresponding openings of the substrate. 熱対流用流路、導入口及び供給路が形成された回転体を備え、前記導入口に導入された液体を前記供給路により前記熱対流用流路に供給し前記熱対流用流路で熱対流させる熱対流生成用チップであって、
前記回転体に、前記導入口に連通する液体受容部が形成され、
前記供給路は、前記液体受容部内の液体を毛細管現象により吸引する吸引通路を有し、
前記吸引通路は、秤量空間を有し、
前記吸引通路は、前記回転体を回転させたときの遠心力により、前記秤量空間内の液体が他の領域内の液体から分離して前記熱対流用流路に供給されよう構成され、
前記遠心力により前記秤量空間内の液体から分離した液体が貯留される余剰液貯留部が、前記回転体に形成されている熱対流生成用チップ。
A thermal convection generating chip comprising a rotor in which a thermal convection flow path, an inlet, and a supply path are formed, the thermal convection generating chip being configured to supply a liquid introduced into the inlet to the thermal convection flow path through the supply path and to cause thermal convection in the thermal convection flow path,
The rotor is provided with a liquid receiving portion communicating with the inlet,
the supply path has a suction passage that draws in the liquid in the liquid receiving portion by capillary action,
The suction passage has a weighing space,
the suction passage is configured so that the liquid in the weighing space is separated from the liquid in other regions by centrifugal force generated when the rotor is rotated, and the liquid is supplied to the thermal convection flow path;
The thermal convection generating chip includes an excess liquid storage section formed on the rotor for storing liquid separated from the liquid in the measuring space by the centrifugal force.
前記余剰液貯留部の流路断面は、丸みがつけられた角部を有する請求項5に記載の熱対流生成用チップ。 The thermal convection generating chip according to claim 5, wherein the flow passage cross section of the excess liquid storage section has rounded corners. 前記余剰液貯留部は、底面から上に突出し両側側面間を横断するダム部を有する請求項5又は請求項6に記載の熱対流生成用チップ。 The chip for generating thermal convection according to claim 5 or 6, wherein the excess liquid storage section has a dam section that protrudes upward from the bottom surface and crosses between both side surfaces. 前記ダム部と前記両側側面とでつくる角部は、丸みがつけられている請求項7に記載の熱対流生成用チップ。 The thermal convection generating chip according to claim 7, wherein the corners formed by the dam portion and both side surfaces are rounded. 熱対流用流路、導入口及び供給路が形成された回転体を備え、前記導入口に導入された液体を前記供給路により前記熱対流用流路に供給し前記熱対流用流路で熱対流させる熱対流生成用チップであって、
前記回転体に、前記供給路とは別に、前記供給路の前記熱対流用流路との接続部に連通した封止剤用空間が形成され、
前記封止剤用空間に常温で固形の封止剤が保持され、
前記供給路により液体が供給された前記熱対流用流路を閉塞するために、前記封止剤用空間の前記封止剤を加温し、溶融させて、前記回転体を回転させたときの遠心力により、前記接続部に移送し充填可能にされている熱対流生成用チップ。
A thermal convection generating chip comprising a rotor in which a thermal convection flow path, an inlet, and a supply path are formed, the thermal convection generating chip being configured to supply a liquid introduced into the inlet to the thermal convection flow path through the supply path and to cause thermal convection in the thermal convection flow path,
a sealant space is formed in the rotor, the sealant space being in communication with a connection portion of the supply path with the thermal convection path, separately from the supply path;
A sealant that is solid at room temperature is held in the sealant space,
A thermal convection generating chip in which the sealant in the sealant space is heated and melted so that the sealant can be transported to and filled in the connection section by centrifugal force generated when the rotor is rotated, in order to block the thermal convection flow path to which liquid is supplied by the supply path.
請求項に記載の熱対流生成用チップを用い、
一つの前記導入口を通して前記液体受容部に、検体及び反応試薬を含有した溶液を導入し、同溶液を複数の前記熱対流用流路に分配供給し、当該各熱対流用流路で熱対流させてポリメラーゼ連鎖反応又は逆転写ポリメラーゼ連鎖反応を行う反応方法。
Using the thermal convection generating chip according to claim 2 ,
A reaction method in which a solution containing a specimen and a reaction reagent is introduced into the liquid receiving section through one of the inlet ports, the solution is distributed and supplied to a plurality of the thermal convection flow paths, and thermal convection is performed in each of the thermal convection flow paths to perform a polymerase chain reaction or a reverse transcription polymerase chain reaction.
JP2021534010A 2019-07-25 2020-07-17 Chip for generating thermal convection and reaction method Active JP7549358B2 (en)

Applications Claiming Priority (3)

Application Number Priority Date Filing Date Title
JP2019136539 2019-07-25
JP2019136539 2019-07-25
PCT/JP2020/027955 WO2021015145A1 (en) 2019-07-25 2020-07-17 Chip for generating thermal convection and reaction method

Publications (3)

Publication Number Publication Date
JPWO2021015145A1 JPWO2021015145A1 (en) 2021-01-28
JPWO2021015145A5 JPWO2021015145A5 (en) 2023-07-27
JP7549358B2 true JP7549358B2 (en) 2024-09-11

Family

ID=74192981

Family Applications (1)

Application Number Title Priority Date Filing Date
JP2021534010A Active JP7549358B2 (en) 2019-07-25 2020-07-17 Chip for generating thermal convection and reaction method

Country Status (2)

Country Link
JP (1) JP7549358B2 (en)
WO (1) WO2021015145A1 (en)

Families Citing this family (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US12050231B2 (en) * 2019-06-03 2024-07-30 Shimadzu Corporation Micro flow path device, testing method using micro flow path device, and testing apparatus using micro flow path device

Citations (7)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2015037255A1 (en) 2013-09-11 2015-03-19 国立大学法人大阪大学 Thermal convection generating chip, thermal convection generating device, and thermal convection generating method
WO2015170753A1 (en) 2014-05-08 2015-11-12 国立大学法人大阪大学 Heat convection-generating chip and liquid-weighing instrument
WO2015174429A1 (en) 2014-05-15 2015-11-19 タカノ株式会社 Analysis chip and sample analysis apparatus
WO2016043196A1 (en) 2014-09-16 2016-03-24 凸版印刷株式会社 Sample analysis chip
WO2016158831A1 (en) 2015-03-30 2016-10-06 コニカミノルタ株式会社 Heat-convection-generating device and heat-convection-generating system
JP2017215288A (en) 2016-06-02 2017-12-07 株式会社フコク Micro flow channel chip
JP2018014966A (en) 2016-07-29 2018-02-01 コニカミノルタ株式会社 Thermal convection generation chip, thermal convection generation unit

Patent Citations (7)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2015037255A1 (en) 2013-09-11 2015-03-19 国立大学法人大阪大学 Thermal convection generating chip, thermal convection generating device, and thermal convection generating method
WO2015170753A1 (en) 2014-05-08 2015-11-12 国立大学法人大阪大学 Heat convection-generating chip and liquid-weighing instrument
WO2015174429A1 (en) 2014-05-15 2015-11-19 タカノ株式会社 Analysis chip and sample analysis apparatus
WO2016043196A1 (en) 2014-09-16 2016-03-24 凸版印刷株式会社 Sample analysis chip
WO2016158831A1 (en) 2015-03-30 2016-10-06 コニカミノルタ株式会社 Heat-convection-generating device and heat-convection-generating system
JP2017215288A (en) 2016-06-02 2017-12-07 株式会社フコク Micro flow channel chip
JP2018014966A (en) 2016-07-29 2018-02-01 コニカミノルタ株式会社 Thermal convection generation chip, thermal convection generation unit

Non-Patent Citations (1)

* Cited by examiner, † Cited by third party
Title
ANAL. CHEM.,2017年,Vol. 89,pp. 12797-12804

Also Published As

Publication number Publication date
WO2021015145A1 (en) 2021-01-28
JPWO2021015145A1 (en) 2021-01-28

Similar Documents

Publication Publication Date Title
US5242606A (en) Sample metering port for analytical rotor having overflow chamber
EP0631126B1 (en) Rotor and method for automatically processing liquids for laboratory and bioanalysis purposes
US9186671B2 (en) Microfluidic test carrier for apportioning a liquid quantity into subquantities
US5242803A (en) Rotor assembly and assay method
JP7549358B2 (en) Chip for generating thermal convection and reaction method
KR102293717B1 (en) Genome Extraction Device with Flow Cover
EP0532591A4 (en) Analytical rotors and methods for analysis of biological fluids
JP6323274B2 (en) Sample analysis chip
KR102486349B1 (en) Amplification Module With a Gas Moving Passage and an Extract Moving Passage
EP4134164B1 (en) Genome extraction device including safety clip combined with inner chamber
KR102346703B1 (en) Genome Extraction Device of Dual Chamber Structure in which the Outer Chamber and the Inner Chamber are combined
US11938478B2 (en) Genome extraction device of dual chamber structure in which outer chamber and bead chamber are combined with each other
KR102577461B1 (en) Chip for Sample Analysis and Sample Analysis Method using the same
JP6714277B2 (en) Chip for heat convection
CA2347669C (en) Analytical rotors and methods for analysis of biological fluids
KR20240059057A (en) All-In-One type cartridge for centrifuge and real-time PCR
KR20240044103A (en) Genome Amplification Module having a branch space adjacent to the extract inlet

Legal Events

Date Code Title Description
A521 Request for written amendment filed

Free format text: JAPANESE INTERMEDIATE CODE: A821

Effective date: 20211110

A711 Notification of change in applicant

Free format text: JAPANESE INTERMEDIATE CODE: A711

Effective date: 20221004

A521 Request for written amendment filed

Free format text: JAPANESE INTERMEDIATE CODE: A821

Effective date: 20221004

A521 Request for written amendment filed

Free format text: JAPANESE INTERMEDIATE CODE: A523

Effective date: 20230714

A621 Written request for application examination

Free format text: JAPANESE INTERMEDIATE CODE: A621

Effective date: 20230714

RD02 Notification of acceptance of power of attorney

Free format text: JAPANESE INTERMEDIATE CODE: A7422

Effective date: 20240612

TRDD Decision of grant or rejection written
A01 Written decision to grant a patent or to grant a registration (utility model)

Free format text: JAPANESE INTERMEDIATE CODE: A01

Effective date: 20240806

A61 First payment of annual fees (during grant procedure)

Free format text: JAPANESE INTERMEDIATE CODE: A61

Effective date: 20240823

R150 Certificate of patent or registration of utility model

Ref document number: 7549358

Country of ref document: JP

Free format text: JAPANESE INTERMEDIATE CODE: R150