JP4615925B2 - Microfluidic device - Google Patents

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JP4615925B2
JP4615925B2 JP2004219587A JP2004219587A JP4615925B2 JP 4615925 B2 JP4615925 B2 JP 4615925B2 JP 2004219587 A JP2004219587 A JP 2004219587A JP 2004219587 A JP2004219587 A JP 2004219587A JP 4615925 B2 JP4615925 B2 JP 4615925B2
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bubbles
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浩一 柴田
正隆 新荻
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Seiko Instruments Inc
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Description

本発明は、微小流路に微量な流体試料を流し流体試料中の特定物質を検出するマイクロ流体装置に関する。   The present invention relates to a microfluidic device that detects a specific substance in a fluid sample by flowing a small amount of fluid sample through a microchannel.

現在、マイクロ化学分析システム（μＴＡＳ）に代表されるマイクロ流体装置が注目されている。マイクロ流体装置では生化学的な分析や反応を微小領域で行うことで、従来型の手法と比較して測定対象となる物質の測定量を少なくし、分析処理時間を大幅に短縮することを可能にしている。また、マイクロ流体装置を医療分野に応用することで、患者から採取する血液などのサンプル量、検査コストを軽減し、検査結果を迅速に提示することができる。   At present, a microfluidic device represented by a microchemical analysis system (μTAS) is attracting attention. Microfluidic devices perform biochemical analysis and reactions in a very small area, reducing the amount of substances to be measured compared to conventional methods and greatly shortening analysis processing time. I have to. In addition, by applying the microfluidic device to the medical field, the amount of sample such as blood collected from a patient and the test cost can be reduced, and the test result can be presented quickly.

上記のようなマイクロ流体装置の一例として特許文献１に示す技術を説明する。図８は従来技術のマイクロ流体装置８０１の概略図である。マイクロ流体装置８０１は、流体試料を装置内に供給する入力ポート８０２、流体試料が流れる微小流路８０３、流体試料の流れを制御するバルブ８０４、流体試料中の特定物質を検出するセンシング部８０５、反応後の流体試料を排出する出力ポート８０６、流体試料を送液するマイクロポンプ８０７からなる。   As an example of the microfluidic device as described above, a technique disclosed in Patent Document 1 will be described. FIG. 8 is a schematic diagram of a prior art microfluidic device 801. The microfluidic device 801 includes an input port 802 that supplies a fluid sample into the device, a micro flow channel 803 through which the fluid sample flows, a valve 804 that controls the flow of the fluid sample, a sensing unit 805 that detects a specific substance in the fluid sample, It comprises an output port 806 for discharging the fluid sample after the reaction, and a micropump 807 for feeding the fluid sample.

また、入力ポート８０２もしくは出力ポート８０６はマイクロポンプ機構８０７と一体化しており、外部装置を用いず送液することを可能にしている。上記マイクロ流体装置８０１では図９に示すように、ＰＤＭＳ（Ｐｏｌｙｄｉｍｅｔｈｙｌｓｉｌａｎｅ）のような自己接着性、通気性を有した弾性部材９０１にμｍオーダーの微小な溝形状（入力ポート９０２、流体試料が流れる微小流路９０３、流体試料の流れを制御するバルブ９０４、流体試料中の特定物質を検出するセンシング部９０５、反応後の流体試料を排出する出力ポート９０６）を加工し、ガラス基板９０７と貼り合わせることで微小流路８０３を形成している。   Further, the input port 802 or the output port 806 is integrated with the micropump mechanism 807, and can send liquid without using an external device. In the microfluidic device 801, as shown in FIG. 9, a micro groove shape (input port 902, a micro fluid through which a fluid sample flows) is formed in an elastic member 901 having self-adhesive properties and air permeability such as PDMS (Polydimethylsilane). A flow path 903, a valve 904 for controlling the flow of the fluid sample, a sensing unit 905 for detecting a specific substance in the fluid sample, and an output port 906 for discharging the fluid sample after the reaction are processed and bonded to the glass substrate 907. Thus, a micro flow path 803 is formed.

このようなマイクロ流体装置８０１の機構では、入力ポート８０２から浸入する大気や、特に負圧で流体試料を送液する際に通気性部材を通って浸入する大気によって微小流路８０３中に気泡が発生する。また流体試料をマイクロ流体装置８０１内で加熱処理する場合などにおいても、流体試料中に溶存の大気が析出し気泡となる。微小流路８０３中で発生した気泡は、センシング部８０５を通過するもしくはセンシング部８０５に停滞する。   In such a mechanism of the microfluidic device 801, bubbles are generated in the microchannel 803 by the atmosphere entering from the input port 802 or the atmosphere entering through the air-permeable member particularly when the fluid sample is fed at a negative pressure. appear. Also when the fluid sample is heat-treated in the microfluidic device 801, the dissolved atmosphere is deposited in the fluid sample to form bubbles. Bubbles generated in the microchannel 803 pass through the sensing unit 805 or stay in the sensing unit 805.

特許文献２では、上記微小流路中に析出した気泡を除去する手段として、微小流路の近傍に設けた減圧式の脱気流路を利用している。図１０は微小流路８０３中で発生した気泡１００１と、減圧式脱気流路１００２との関係図である。また、微小流路８０３と減圧式脱気流路１００２間は通気性部材１００３で形成されている。微小流路８０３で発生した気泡１００１は通気性部材１００３を通って減圧式脱気流路１００２に移る機構となっている。
特開２００４−１０８２８５ 特開２００２-０１８２７１ In Patent Document 2, a depressurization type deaeration channel provided in the vicinity of the micro channel is used as means for removing bubbles deposited in the micro channel. FIG. 10 is a diagram showing the relationship between the bubble 1001 generated in the micro flow path 803 and the decompression type deaeration flow path 1002. Further, the air passage member 1003 is formed between the micro flow path 803 and the decompression type deaeration flow path 1002. A bubble 1001 generated in the minute channel 803 passes through the air-permeable member 1003 and moves to the decompression type deaeration channel 1002.
JP 2004-108285 A JP2002-018271

マイクロ流体装置８０１の機構では、入力ポート８０２から浸入する大気や、特に負圧で流体試料を送液する際に通気性部材を通って浸入する大気によって微小流路８０３中に気泡が発生してしまう。また流体試料をマイクロ流体装置８０１内で加熱処理する場合などにおいても、流体試料中に溶存の大気が析出し気泡となる。特許文献２のような微小流路８０３と減圧式脱気流路１００２の関係では特に流体試料の流速が大きい場合などに、気泡１００１が減圧式脱気流路１００２周辺を通過してしまうため、気泡１００１の全てを除去することが困難であるという問題がある。微小流路８０３中で発生した気泡は、センシング部８０５を通過するもしくはセンシング部８０５に停滞する。 In the mechanism of the microfluidic device 801, bubbles are generated in the microchannel 803 by the atmosphere entering from the input port 802, or the atmosphere entering through the air-permeable member when the fluid sample is sent at a negative pressure. End up. Also when the fluid sample is heat-treated in the microfluidic device 801, the dissolved atmosphere is deposited in the fluid sample to form bubbles. In the relationship between the micro flow path 803 and the depressurization type degassing flow path 1002 as in Patent Document 2, the bubble 1001 passes through the periphery of the depressurization type degassing flow path 1002 especially when the flow rate of the fluid sample is large. There is a problem that it is difficult to remove all of the above. Bubbles generated in the microchannel 803 pass through the sensing unit 805 or stay in the sensing unit 805.

センシング部８０５では流体試料中の特定物質を検出するために極微小なエネルギー変化を測定する必要があるが、気泡がセンシング部８０５に存在するとノイズとして不必要な信号を検出させてしまう。また、微小流路８０３中に気泡が存在すると流体試料の流れの速度分布が著しく乱れるために流量の制御を行うことが困難になるという問題が起こる。   The sensing unit 805 needs to measure a very small energy change in order to detect a specific substance in the fluid sample. However, if bubbles exist in the sensing unit 805, an unnecessary signal as noise is detected. In addition, if bubbles are present in the microchannel 803, the flow velocity distribution of the fluid sample is significantly disturbed, which makes it difficult to control the flow rate.

そこで本発明においては、微小流路中で化学的な分析や反応を行うマイクロ流体装置において、送液時に入力ポートや微小流路形成部材から浸入する大気、もしくは溶存空気によって発生する微小流路中の気泡をセンシング部に到達する以前に全て捕獲し、除去することを目的とする。   Therefore, in the present invention, in a microfluidic device that performs chemical analysis or reaction in a microchannel, in the microchannel generated by the atmosphere that enters from the input port or the microchannel forming member during liquid feeding or dissolved air The purpose is to capture and remove all the bubbles before reaching the sensing part.

上記のような課題を解決するため本発明においては、マイクロ流体装置内の微小流路、特にセンシング部に到達する手前に設けた減圧式脱気流路周辺の微小流路を流体試料の流れが淀むような形状とした。このような微小流路形状にすることで、入力ポートや微小流路形成部材から浸入する大気、もしくは溶存空気によって発生する微小流路中の気泡を捕獲することができる。微小流路と減圧式脱気流路間は通気性部材で形成されているか、もしくは極微細流路が加工されており、それらを介して微小流路中の気泡が減圧式脱気流路側へと移され、気泡は微小流路から除去される。   In order to solve the problems as described above, in the present invention, the flow of the fluid sample occupies the microchannel in the microfluidic device, particularly the microchannel around the decompression type deaeration channel provided before reaching the sensing unit. The shape was as follows. By adopting such a microchannel shape, it is possible to capture bubbles in the microchannel generated by the atmosphere entering from the input port or the microchannel forming member or dissolved air. Between the microchannel and the depressurization type deaeration channel, it is formed of a breathable member, or the ultrafine channel is processed, through which the bubbles in the microchannel are transferred to the depressurization type deaeration channel side The bubbles are removed from the microchannel.

本発明では、微小流路中で生化学的な分析や反応を行う、マイクロ流体装置内の微小流路、特にセンシング部に到達する手前に設けた減圧式脱気流路周辺の微小流路を流体試料の流れが淀むような形状とした。微小流路中の流体試料の流れが淀む形状部分では、入力ポートや微小流路形成部材から浸入する大気、もしくは溶存空気によって発生する微小流路中の気泡を捕獲することができる。微小流路と減圧式脱気流路間は、通気性部材で形成されているか、もしくは極微細流路が加工されており、それらを介して微小流路中の気泡が減圧式脱気流路側へと移され、気泡は微小流路から除去される。   In the present invention, a microchannel in a microfluidic device that performs biochemical analysis and reaction in a microchannel, particularly a microchannel around a decompression type deaeration channel provided before reaching the sensing unit is fluidized. The shape was such that the sample flow was stagnant. In the shape portion where the flow of the fluid sample in the microchannel is stagnant, bubbles in the microchannel generated by the atmosphere entering from the input port or the microchannel forming member or dissolved air can be captured. Between the microchannel and the depressurization type deaeration channel, it is formed by a gas permeable member, or an ultrafine channel is processed, through which the bubbles in the microchannel move to the depressurization type deaeration channel side. The bubbles are removed from the microchannel.

この結果、発生した気泡は減圧式脱気流路周辺を通過してセンシング部に到達することなく、ほとんど全てが除去される。気泡を取り除いたことでセンシングの際に発生するノイズが無くなり、高精度かつ正確な特定物質の検出を行うことができる。さらに、気泡による流体試料の速度分布変化が解消され、流量の制御を容易に行うことができるようになる。   As a result, almost all of the generated bubbles are removed without passing through the periphery of the decompression type deaeration channel and reaching the sensing unit. By removing the bubbles, noise generated during sensing is eliminated, and a specific substance can be detected with high accuracy and accuracy. Furthermore, the change in velocity distribution of the fluid sample due to bubbles is eliminated, and the flow rate can be easily controlled.

実施の形態１Embodiment 1

図１は、本発明の実施の形態１における微小流路中で生化学的な分析や反応を行うマイクロ流体装置１０１の概略図である。１０２は流体試料を装置内に送り込む入力ポート、１０３は流体試料が流れる微小流路、１０４は流体試料の流れを制御するバルブ、１０５は流体試料中の特定物質を検出するセンシング部、１０６はセンシングが終了した流体試料を廃液する出力ポート、１０７は流体試料を送液するポンプである。また、１０８は減圧式脱気用流路、１０９は気泡捕獲部である。   FIG. 1 is a schematic diagram of a microfluidic device 101 that performs biochemical analysis and reaction in a microchannel according to Embodiment 1 of the present invention. 102 is an input port for feeding the fluid sample into the apparatus, 103 is a micro flow channel through which the fluid sample flows, 104 is a valve for controlling the flow of the fluid sample, 105 is a sensing unit for detecting a specific substance in the fluid sample, and 106 is sensing. The output port 107 for draining the fluid sample after the completion of the operation is a pump 107 for feeding the fluid sample. Reference numeral 108 denotes a pressure reducing degassing flow path, and 109 denotes a bubble capturing unit.

流体試料は入力ポート１０２から必要量が微小流路１０３内に送り込まれ、微小流路１０３中を負圧で送液している。このとき入力ポート１０２では流体試料中に大気が混じり込むため、微小流路１０３中には大気が浸入してしまう。また、微小流路１０３を通気性部材で形成した場合などは、その通気性部材を通過して微小流路中に大気が浸入する。このようにして浸入してきた大気は微小流路１０３中で気泡となる。特にセンシング部１０５における微小流路１０３では形状が大きく変化しており、流体試料の流れが淀む箇所ができる。   A necessary amount of the fluid sample is fed from the input port 102 into the microchannel 103 and is fed through the microchannel 103 at a negative pressure. At this time, since air is mixed in the fluid sample at the input port 102, the air enters the microchannel 103. In addition, when the micro flow path 103 is formed of a gas permeable member, air enters the micro flow path through the gas permeable member. The air that has entered in this way becomes bubbles in the microchannel 103. In particular, the shape of the microchannel 103 in the sensing unit 105 is greatly changed, and a portion where the flow of the fluid sample is stagnated is formed.

そして発生した気泡２０１はセンシング部１０５まで到達した後、流体試料の流れが淀む箇所に停滞してしまう。また、微小流路１０５を通気性部材で形成した場合、流体試料の流れが淀んでいる箇所に停滞した気泡２０１は通気性部材を通過してくる大気によって容積を増やし続けることになる。このためセンシング部１０５から気泡２０１が消え去ることはない。センシング部１０５に気泡が存在するとノイズとなり不必要な信号を検出させてしまうため検出精度の低下を招く。したがって、微小流路１０３で発生した気泡２０１はセンシング部１０５に到達する前に除去してしまう必要がある。   Then, after the generated bubble 201 reaches the sensing unit 105, the bubble 201 stays at a place where the flow of the fluid sample is stagnant. In addition, when the microchannel 105 is formed of a gas permeable member, the bubbles 201 stagnated at a place where the flow of the fluid sample is stagnated continue to increase in volume due to the atmosphere passing through the gas permeable member. For this reason, the bubble 201 does not disappear from the sensing unit 105. If bubbles exist in the sensing unit 105, noise is detected and an unnecessary signal is detected, resulting in a decrease in detection accuracy. Therefore, it is necessary to remove the bubbles 201 generated in the microchannel 103 before reaching the sensing unit 105.

そこで本実施例では、センシング部１０５より手前の微小流路１０３の近傍に脱気用流路１０８を設けている。さらに、微小流路の形状を１０９のように変え微小流路の側壁付近で流速を変化させることで、流体試料の流れに淀みが発生するような気泡捕獲部１０９を形成している。   Therefore, in this embodiment, a deaeration channel 108 is provided in the vicinity of the microchannel 103 in front of the sensing unit 105. Further, by changing the shape of the microchannel as shown by 109 and changing the flow velocity near the side wall of the microchannel, the bubble capturing unit 109 that causes stagnation in the flow of the fluid sample is formed.

図２はセンシング部１０５の近傍部分を拡大して示す拡大図である。また、センシング部１０５より手前の微小流路１０３、気泡捕獲部１０９は通気性を有した部材で形成されている。まず、入力ポート１０２などから浸入した気泡は、気泡捕獲部１０９の流体試料の流れが淀んでいる箇所で止まり停滞する。減圧式脱気流路１０８は微小流路１０３中を送液する負圧よりもさらに減圧してあり、気泡捕獲部１０９に停滞した気泡２０１は周辺の通気性部材を通って減圧式脱気流路１０８へと移る。この結果、微小流路１０３中から気泡２０１は消え去りセンシング部１０５に送られるのは流体試料のみとなったことを確認した。   FIG. 2 is an enlarged view showing the vicinity of the sensing unit 105 in an enlarged manner. Further, the micro channel 103 and the bubble capturing unit 109 in front of the sensing unit 105 are formed of a member having air permeability. First, bubbles that have entered from the input port 102 or the like stop and stagnate at a place where the flow of the fluid sample in the bubble capturing unit 109 is stagnant. The depressurization type deaeration channel 108 is further depressurized than the negative pressure sent through the micro channel 103, and the bubbles 201 stagnated in the bubble trapping part 109 pass through the surrounding air-permeable member and the depressurization type deaeration channel 108. Move on. As a result, it was confirmed that the bubbles 201 disappeared from the microchannel 103 and only the fluid sample was sent to the sensing unit 105.

図１１はセンシング部１０５において特定物質の反応エネルギーを検出した結果であり、検出時間と信号強度の関係を表す。横軸１１０１は検出時間、縦軸１１０２は信号強度、実線１１０３は減圧式脱気流路１０８を設けた場合のセンシング部１０５の信号、破線１１０４は減圧式脱気流路１０８が無い場合のセンシング部１０５の信号、横軸１１０２上の点１１０５は流体試料がセンシング部１０５に到達した時間である。減圧式脱気流路１０８が無い場合では気泡２０１が要因となるノイズが発生しており、気泡２０１によって反応が遅れる分検出速度が低下した。一方、減圧式脱気流路１０８を設けた場合においては、気泡によるノイズが発生せず、検出速度の低下も見られなかった。したがって、センシング部１０５では気泡２０１による検出速度、検出精度の低下が無い正確な特定物質の検出を行うことができた。   FIG. 11 shows the result of detecting the reaction energy of the specific substance in the sensing unit 105, and shows the relationship between the detection time and the signal intensity. The horizontal axis 1101 is the detection time, the vertical axis 1102 is the signal intensity, the solid line 1103 is the signal of the sensing unit 105 when the decompression type deaeration channel 108 is provided, and the broken line 1104 is the sensing unit 105 when there is no decompression type deaeration channel 108. The point 1105 on the horizontal axis 1102 is the time when the fluid sample reaches the sensing unit 105. In the absence of the depressurization type deaeration channel 108, noise caused by the bubbles 201 was generated, and the detection speed was lowered due to the reaction being delayed by the bubbles 201. On the other hand, when the depressurization type deaeration channel 108 was provided, no noise was generated due to bubbles, and no decrease in the detection speed was observed. Therefore, the sensing unit 105 was able to accurately detect a specific substance without a decrease in detection speed and detection accuracy due to the bubbles 201.

実施の形態２Embodiment 2

図３は、本発明の実施の形態２における微小流路中で生化学的な分析や反応を行うマイクロ流体装置１０１の概略図である。１０２は流体試料を装置内に送り込む入力ポート、１０３は流体試料が流れる微小流路、１０４は流体試料の流れを制御するバルブ、１０５は流体試料中の特定物質を検出するセンシング部、１０６はセンシングが終了した流体試料を廃液する出力ポート、１０７は流体試料を送液するポンプである。   FIG. 3 is a schematic diagram of a microfluidic device 101 that performs biochemical analysis and reaction in a microchannel according to Embodiment 2 of the present invention. 102 is an input port for feeding the fluid sample into the apparatus, 103 is a micro flow channel through which the fluid sample flows, 104 is a valve for controlling the flow of the fluid sample, 105 is a sensing unit for detecting a specific substance in the fluid sample, and 106 is sensing. The output port 107 for draining the fluid sample after the completion of the operation is a pump 107 for feeding the fluid sample.

また、１０８は減圧式脱気用流路、１０９は気泡捕獲部である。流体試料は入力ポート１０２から必要量が微小流路１０３内に送り込まれ、微小流路１０３中を負圧で送液している。このとき入力ポート１０２では流体試料中に大気が混じり込むため、微小流路１０３中には大気が浸入してしまう。また、微小流路１０３を通気性部材で形成した場合などは、その通気性部材を通過して微小流路中に大気が浸入する。このようにして浸入してきた大気は微小流路１０３中で気泡となる。   Reference numeral 108 denotes a pressure reducing degassing flow path, and 109 denotes a bubble capturing unit. A necessary amount of the fluid sample is fed from the input port 102 into the microchannel 103 and is fed through the microchannel 103 at a negative pressure. At this time, since air is mixed in the fluid sample at the input port 102, the air enters the microchannel 103. In addition, when the micro flow path 103 is formed of a gas permeable member, air enters the micro flow path through the gas permeable member. The air that has entered in this way becomes bubbles in the microchannel 103.

特にセンシング部１０５における微小流路１０３では形状が大きく変化しており、流体試料の流れが淀む箇所ができる。そして発生した気泡２０１はセンシング部１０５まで到達した後、流体試料の流れが淀む箇所に停滞してしまう。また、微小流路１０５を通気性部材で形成した場合、流体試料の流れが淀んでいる箇所に停滞した気泡２０１は通気性部材を通過してくる大気によって容積を増やし続けることになる。このためセンシング部１０５から気泡２０１が消え去ることはない。センシング部１０５に気泡が存在するとノイズとなり不必要な信号を検出させてしまうため検出精度の低下を招く。   In particular, the shape of the microchannel 103 in the sensing unit 105 is greatly changed, and a portion where the flow of the fluid sample is stagnated is formed. Then, after the generated bubble 201 reaches the sensing unit 105, the bubble 201 stays at a place where the flow of the fluid sample is stagnant. In addition, when the microchannel 105 is formed of a gas permeable member, the bubbles 201 stagnated at a place where the flow of the fluid sample is stagnated continue to increase in volume due to the atmosphere passing through the gas permeable member. For this reason, the bubble 201 does not disappear from the sensing unit 105. If bubbles exist in the sensing unit 105, noise is detected and an unnecessary signal is detected, resulting in a decrease in detection accuracy.

したがって、微小流路１０３で発生した気泡２０１はセンシング部１０５に到達する前に除去してしまう必要がある。そこで本実施例では、センシング部１０５より手前の微小流路１０３の近傍に脱気用流路１０８を設けている。さらに、微小流路の形状を１０９のように変え微小流路の側壁付近で流速を変化させることで、流体試料の流れに淀みが発生するような気泡捕獲部１０９を形成している。   Therefore, it is necessary to remove the bubbles 201 generated in the microchannel 103 before reaching the sensing unit 105. Therefore, in this embodiment, a deaeration channel 108 is provided in the vicinity of the microchannel 103 in front of the sensing unit 105. Further, by changing the shape of the microchannel as shown by 109 and changing the flow velocity near the side wall of the microchannel, the bubble capturing unit 109 that causes stagnation in the flow of the fluid sample is formed.

図４は微小流路１０３中で発生した気泡２０１と、減圧式脱気流路１０８、気泡捕獲部１０９との配置関係を拡大して示す拡大図である。また、センシング部１０５より手前の微小流路１０３、気泡捕獲部１０９は通気性を有した部材で形成されている。まず、入力ポート１０２などから浸入した気泡２０１は、気泡捕獲部１０９の流体試料の流れが淀んでいる箇所で、止まり停滞する。減圧式脱気流路１０８は微小流路１０３中を送液する負圧よりもさらに減圧してあり、気泡捕獲部１０９に停滞した気泡２０１は周辺の通気性部材を通って減圧式脱気流路１０８へと移る。さらに、本実施例においては気泡捕獲部１０９を連続させて設けることで、気泡２０１が捕獲されずセンシング部１０５まで到達してしまうことを防いでいる。   FIG. 4 is an enlarged view showing the arrangement relationship between the bubbles 201 generated in the micro flow channel 103, the decompression type deaeration flow channel 108, and the bubble capturing unit 109 in an enlarged manner. Further, the micro channel 103 and the bubble capturing unit 109 in front of the sensing unit 105 are formed of a member having air permeability. First, the bubble 201 that has entered from the input port 102 or the like stops and stagnates at a location where the flow of the fluid sample in the bubble capturing unit 109 is stagnant. The depressurization type deaeration channel 108 is further depressurized than the negative pressure sent through the micro channel 103, and the bubbles 201 stagnated in the bubble trapping part 109 pass through the surrounding air-permeable member and the depressurization type deaeration channel 108. Move on. Furthermore, in the present embodiment, the bubble capturing unit 109 is continuously provided to prevent the bubbles 201 from reaching the sensing unit 105 without being captured.

この結果、微小流路１０３中から気泡２０１は消え去りセンシング部１０５に送られるのは流体試料のみとなったことを確認した。図１１はセンシング部１０５において特定物質の反応エネルギーを検出した結果であり、検出時間と信号強度の関係を表す。横軸１１０１は検出時間、縦軸１１０２は信号強度、実線１１０３は減圧式脱気流路１０８を設けた場合のセンシング部１０５の信号、破線１１０４は減圧式脱気流路１０８が無い場合のセンシング部１０５の信号、横軸１１０２上の点１１０５は流体試料がセンシング部１０５に到達した時間である。減圧式脱気流路１０８が無い場合では気泡２０１が要因となるノイズが発生しており、気泡２０１によって反応が遅れる分検出速度が低下した。一方、減圧式脱気流路１０８を設けた場合においては、気泡によるノイズが発生せず、検出速度の低下も見られなかった。したがって、センシング部１０５では気泡２０１による検出速度、検出精度の低下が無い正確な特定物質の検出を行うことができた。   As a result, it was confirmed that the bubbles 201 disappeared from the microchannel 103 and only the fluid sample was sent to the sensing unit 105. FIG. 11 shows the result of detecting the reaction energy of the specific substance in the sensing unit 105, and shows the relationship between the detection time and the signal intensity. The horizontal axis 1101 is the detection time, the vertical axis 1102 is the signal intensity, the solid line 1103 is the signal of the sensing unit 105 when the decompression type deaeration channel 108 is provided, and the broken line 1104 is the sensing unit 105 when there is no decompression type deaeration channel 108. The point 1105 on the horizontal axis 1102 is the time when the fluid sample reaches the sensing unit 105. In the absence of the depressurization type deaeration channel 108, noise caused by the bubbles 201 was generated, and the detection speed was lowered due to the reaction being delayed by the bubbles 201. On the other hand, when the depressurization type deaeration channel 108 was provided, no noise was generated due to bubbles, and no decrease in the detection speed was observed. Therefore, the sensing unit 105 was able to accurately detect a specific substance without a decrease in detection speed and detection accuracy due to the bubbles 201.

実施の形態３Embodiment 3

図５は、本発明の実施の形態３における微小流路中で生化学的な分析や反応を行うマイクロ流体装置１０１の概略図である。１０２は流体試料を装置内に送り込む入力ポート、１０３は流体試料が流れる微小流路、１０４は流体試料の流れを制御するバルブ、１０５は流体試料中の特定物質を検出するセンシング部、１０６はセンシングが終了した流体試料を廃液する出力ポート、１０７は流体試料を送液するポンプである。また、１０８は減圧式脱気用流路、１０９は気泡捕獲部である。   FIG. 5 is a schematic diagram of a microfluidic device 101 that performs biochemical analysis and reaction in a microchannel according to Embodiment 3 of the present invention. 102 is an input port for feeding the fluid sample into the apparatus, 103 is a micro flow channel through which the fluid sample flows, 104 is a valve for controlling the flow of the fluid sample, 105 is a sensing unit for detecting a specific substance in the fluid sample, and 106 is sensing. The output port 107 for draining the fluid sample after the completion of the operation is a pump 107 for feeding the fluid sample. Reference numeral 108 denotes a pressure reducing degassing flow path, and 109 denotes a bubble capturing unit.

流体試料は入力ポート１０２から必要量が微小流路１０３内に送り込まれ、微小流路１０３中を負圧で送液している。このとき入力ポート１０２では流体試料中に大気が混じり込むため、微小流路１０３中には大気が浸入してしまう。また、微小流路１０３を通気性部材で形成した場合などは、その通気性部材を通過して微小流路中に大気が浸入する。このようにして浸入してきた大気は微小流路１０３中で気泡となる。特にセンシング部１０５における微小流路１０３では形状が大きく変化しており、流体試料の流れが淀む箇所ができる。   A necessary amount of the fluid sample is fed from the input port 102 into the microchannel 103 and is fed through the microchannel 103 at a negative pressure. At this time, since air is mixed in the fluid sample at the input port 102, the air enters the microchannel 103. In addition, when the micro flow path 103 is formed of a gas permeable member, air enters the micro flow path through the gas permeable member. The air that has entered in this way becomes bubbles in the microchannel 103. In particular, the shape of the microchannel 103 in the sensing unit 105 is greatly changed, and a portion where the flow of the fluid sample is stagnated is formed.

そして発生した気泡２０１はセンシング部１０５まで到達した後、流体試料の流れが淀む箇所に停滞してしまう。また、微小流路１０５を通気性部材で形成した場合、流体試料の流れが淀んでいる箇所に停滞した気泡２０１は通気性部材を通過してくる大気によって容積を増やし続けることになる。このためセンシング部１０５から気泡２０１が消え去ることはない。センシング部１０５に気泡２０１が存在するとノイズとなり不必要な信号を検出させてしまうため検出精度の低下を招く。したがって、微小流路１０３で発生した気泡２０１はセンシング部１０５に到達する前に除去してしまう必要がある。   Then, after the generated bubble 201 reaches the sensing unit 105, the bubble 201 stays at a place where the flow of the fluid sample is stagnant. In addition, when the microchannel 105 is formed of a gas permeable member, the bubbles 201 stagnated at a place where the flow of the fluid sample is stagnated continue to increase in volume due to the atmosphere passing through the gas permeable member. For this reason, the bubble 201 does not disappear from the sensing unit 105. If the bubble 201 exists in the sensing unit 105, noise is detected and an unnecessary signal is detected, which causes a decrease in detection accuracy. Therefore, it is necessary to remove the bubbles 201 generated in the microchannel 103 before reaching the sensing unit 105.

そこで本実施例では、センシング部１０５より手前の微小流路１０３の近傍に脱気用流路１０８を設けている。さらに、微小流路の形状を１０９のように変え微小流路の側壁付近で流速を変化させることで、流体試料の流れに淀みが発生するような気泡捕獲部１０９を形成している。   Therefore, in this embodiment, a deaeration channel 108 is provided in the vicinity of the microchannel 103 in front of the sensing unit 105. Further, by changing the shape of the microchannel as shown by 109 and changing the flow velocity near the side wall of the microchannel, the bubble capturing unit 109 that causes stagnation in the flow of the fluid sample is formed.

図６は微小流路１０３中で発生した気泡２０１と、減圧式脱気流路１０８、気泡捕獲部１０９との配置関係を拡大して示す拡大図である。また、センシング部１０５より手前の微小流路１０３、気泡捕獲部５０１は通気性を有した部材で形成されている。まず、入力ポート１０２などから浸入した気泡２０１は、気泡捕獲部１０９の流体試料が淀んでいる箇所で、止まり停滞する。減圧式脱気流路１０８は微小流路１０３中を送液する負圧よりもさらに減圧してあり、気泡捕獲部１０９に停滞した気泡２０１は周辺の通気性部材を通って減圧式脱気流路１０８へと移る。さらに、本実施例においては微小流路１０３と気泡捕獲部１０９の中心を結ぶ線が直線ではなく、蛇行させていることで気泡２０１を捕獲しやすくしセンシング部１０５まで到達してしまうことを防いでいる。   FIG. 6 is an enlarged view showing, in an enlarged manner, the positional relationship among the bubbles 201 generated in the microchannel 103, the decompression-type deaeration channel 108, and the bubble capturing unit 109. Further, the microchannel 103 and the bubble capturing unit 501 in front of the sensing unit 105 are formed of a member having air permeability. First, the bubble 201 that has entered from the input port 102 or the like stops and stagnates at a place where the fluid sample in the bubble capturing unit 109 is trapped. The depressurization type deaeration channel 108 is further depressurized than the negative pressure sent through the micro channel 103, and the bubbles 201 stagnated in the bubble trapping part 109 pass through the surrounding air-permeable member and the depressurization type deaeration channel 108. Move on. Furthermore, in the present embodiment, the line connecting the microchannel 103 and the center of the bubble capturing unit 109 is not a straight line, but meandering makes it easy to capture the bubble 201 and prevents it from reaching the sensing unit 105. It is out.

この結果、微小流路１０３中から気泡２０１は消え去りセンシング部１０５に送られるのは流体試料のみとなったことを確認した。図１１はセンシング部１０５において特定物質の反応エネルギーを検出した結果であり、検出時間と信号強度の関係を表す。横軸１１０１は検出時間、縦軸１１０２は信号強度、実線１１０３は減圧式脱気流路１０８を設けた場合のセンシング部１０５の信号、破線１１０４は減圧式脱気流路１０８が無い場合のセンシング部１０５の信号、横軸１１０２上の点１１０５は流体試料がセンシング部１０５に到達した時間である。減圧式脱気流路１０８が無い場合では気泡２０１が要因となるノイズが発生しており、気泡２０１によって反応が遅れる分検出速度が低下した。一方、減圧式脱気流路１０８を設けた場合においては、気泡２０１によるノイズが発生せず、検出速度の低下も見られなかった。したがって、センシング部１０５では気泡２０１による検出速度、検出精度の低下が無い正確な特定物質の検出を行うことができた。   As a result, it was confirmed that the bubbles 201 disappeared from the microchannel 103 and only the fluid sample was sent to the sensing unit 105. FIG. 11 shows the result of detecting the reaction energy of the specific substance in the sensing unit 105, and shows the relationship between the detection time and the signal intensity. The horizontal axis 1101 is the detection time, the vertical axis 1102 is the signal intensity, the solid line 1103 is the signal of the sensing unit 105 when the decompression type deaeration channel 108 is provided, and the broken line 1104 is the sensing unit 105 when there is no decompression type deaeration channel 108. The point 1105 on the horizontal axis 1102 is the time when the fluid sample reaches the sensing unit 105. In the absence of the depressurization type deaeration channel 108, noise caused by the bubbles 201 was generated, and the detection speed was lowered due to the reaction being delayed by the bubbles 201. On the other hand, when the decompression type deaeration channel 108 was provided, noise due to the bubbles 201 was not generated, and the detection speed was not reduced. Therefore, the sensing unit 105 was able to accurately detect a specific substance without a decrease in detection speed and detection accuracy due to the bubbles 201.

実施の形態４Embodiment 4

図７は、図２における気泡２０１と微小流路１０３、脱気用流路１０８，気泡捕獲部１０９，極微細流路７０１の配置関係を拡大して示す拡大図である。前記の本発明の実施の形態１、２、３におけるマイクロ流体装置１０１においては、通気性部材を通して微小流路中の気泡２０１の除去を行っていたが、本発明の実施の形態においては微小流路と脱気用流路間は通気性部材ではなく、直径約１μｍ以下の極微細な流路を通して脱気を行っている。   FIG. 7 is an enlarged view showing, in an enlarged manner, the positional relationship between the bubble 201 and the microchannel 103, the deaeration channel 108, the bubble trap 109, and the ultrafine channel 701 in FIG. In the microfluidic devices 101 according to the first, second, and third embodiments of the present invention, the bubbles 201 in the microchannels are removed through the air-permeable member. However, in the embodiments of the present invention, the microfluidic devices 101 are used. Deaeration is performed between the path and the deaeration channel through a very fine channel having a diameter of about 1 μm or less, not a breathable member.

このような極微細サイズの流路は、ある圧力以下において液体を通さず気体のみを通す性質を有す。センシング部１０５やセンシング部１０５に到達する手前の微小流路１０３に設けた流れが淀むような気泡捕獲部１０９では気泡２０１が溜まることが前もって把握できるため、この部分に極微細流路７０１を設けて集中的に脱気を行う。   Such an ultrafine channel has a property of allowing only gas to pass through at a certain pressure or lower without passing liquid. Since it is possible to grasp in advance that bubbles 201 accumulate in the bubble capturing unit 109 in which the flow provided in the sensing unit 105 or the microchannel 103 before reaching the sensing unit 105 is stagnant, an ultrafine channel 701 is provided in this portion. Degassing intensively.

この結果、微小流路１０３中から気泡２０１は消え去りセンシング部１０５に送られるのは流体試料のみとなったことを確認した。図１１はセンシング部１０５において特定物質の反応エネルギーを検出した結果であり、検出時間と信号強度の関係を表す。横軸１１０１は検出時間、縦軸１１０２は信号強度、実線１１０３は減圧式脱気流路１０８を設けた場合のセンシング部１０５の信号、破線１１０４は減圧式脱気流路１０８が無い場合のセンシング部１０５の信号、横軸１１０２上の点１１０５は流体試料がセンシング部１０５に到達した時間である。   As a result, it was confirmed that the bubbles 201 disappeared from the microchannel 103 and only the fluid sample was sent to the sensing unit 105. FIG. 11 shows the result of detecting the reaction energy of the specific substance in the sensing unit 105, and shows the relationship between the detection time and the signal intensity. The horizontal axis 1101 is the detection time, the vertical axis 1102 is the signal intensity, the solid line 1103 is the signal of the sensing unit 105 when the decompression type deaeration channel 108 is provided, and the broken line 1104 is the sensing unit 105 when there is no decompression type deaeration channel 108. The point 1105 on the horizontal axis 1102 is the time when the fluid sample reaches the sensing unit 105.

減圧式脱気流路１０８が無い場合では気泡２０１が要因となるノイズが発生しており、気泡２０１によって反応が遅れる分検出速度が低下した。一方、減圧式脱気流路１０８を設けた場合においては、気泡によるノイズが発生せず、検出速度の低下も見られなかった。したがって、センシング部１０５では気泡２０１による検出速度、検出精度の低下が無い正確な特定物質の検出を行うことができた。   In the absence of the depressurization type deaeration channel 108, noise caused by the bubbles 201 was generated, and the detection speed was lowered due to the reaction being delayed by the bubbles 201. On the other hand, when the depressurization type deaeration channel 108 was provided, no noise was generated due to bubbles, and no decrease in the detection speed was observed. Therefore, the sensing unit 105 was able to accurately detect a specific substance without a decrease in detection speed and detection accuracy due to the bubbles 201.

本発明の実施形態１におけるマイクロ流体装置の概略図Schematic of the microfluidic device in Embodiment 1 of the present invention 本発明の実施形態１における微小流路と脱気用流路の拡大図The enlarged view of the micro channel in Embodiment 1 of this invention, and the channel for deaeration 本発明の実施形態２におけるマイクロ流体装置の概略図Schematic of the microfluidic device in Embodiment 2 of the present invention 本発明の実施形態２における微小流路と気泡捕獲部の拡大図Enlarged view of micro flow channel and bubble capture unit in embodiment 2 of the present invention 本発明の実施形態３におけるマイクロ流体装置の概略図Schematic of the microfluidic device in Embodiment 3 of the present invention 本発明の実施形態３における微小流路と気泡捕獲部の拡大図Enlarged view of microchannel and bubble trapping part in Embodiment 3 of the present invention 本発明の実施形態４における微小流路と気泡捕獲部の拡大図Enlarged view of microchannel and bubble trapping portion in Embodiment 4 of the present invention 従来のマイクロ流体装置の概略図Schematic diagram of a conventional microfluidic device 従来のマイクロ流体装置の作製方法Manufacturing method of conventional microfluidic device 従来のマイクロ流体装置の概略図Schematic diagram of a conventional microfluidic device 本発明の実施例におけるセンシング部の検出信号の経時変化Change with time of detection signal of sensing unit in an embodiment of the present invention

符号の説明Explanation of symbols

１０１、８０１ マイクロ流体装置
１０２、８０２、９０２ 入力ポート
１０３、８０３、９０３ 微小流路
１０４、８０４、９０４ バルブ
１０５、８０５、９０５ センシング部
１０６、８０６、９０６ 出力ポート
１０７、８０７ マイクロポンプ
１０８、１００３ 圧式脱気流路
１０９ 気泡捕獲部
２０１、１００１ 気泡
７０１ 極微細流路
９０１ ＰＤＭＳ
９０７ ガラス基板
１００３ 通気性部材
１１０１ 検出時間
１１０２ 信号強度
１１０３ 減圧式脱気流路１０８を設けた場合のセンシング部１０５の信号
１１０４ 減圧式脱気流路１０８が無い場合のセンシング部１０５の信号
１１０５ 流体試料がセンシング部に到達した時間 101, 801 Microfluidic device 102, 802, 902 Input port 103, 803, 903 Micro flow path 104, 804, 904 Valve 105, 805, 905 Sensing unit 106, 806, 906 Output port 107, 807 Micro pump 108, 1003 Pressure type Deaeration channel 109 Bubble capture unit 201, 1001 Bubble 701 Ultrafine channel 901 PDMS
907 Glass substrate 1003 Breathable member 1101 Detection time 1102 Signal intensity 1103 Signal 1104 of sensing unit 105 when decompression-type deaeration channel 108 is provided Signal 1105 of sensing unit 105 when decompression-type deaeration channel 108 is not present Time to reach the sensing unit

Claims (7)

微小流路中で生化学的な分析や反応を行うマイクロ流体装置において、
前記微小流路中に流体の流れが淀む構造を備える気泡捕獲部と、
前記気泡捕獲部近傍に、前記微小流路中に析出した気泡を除去して脱気する脱気手段とを備え、
前記気泡捕獲部は、前記微小流路よりも幅広な構造であることを特徴とするマイクロ流体装置。 In microfluidic devices that perform biochemical analysis and reactions in microchannels,
A bubble capture unit having a structure in which a fluid flow is contained in the microchannel;
In the vicinity of the bubble capture unit, comprising a deaeration means for degassing by removing the bubbles deposited in the microchannel ,
The microfluidic device , wherein the bubble trapping part has a structure wider than the microchannel. 微小流路中で生化学的な分析や反応を行うマイクロ流体装置において、In microfluidic devices that perform biochemical analysis and reactions in microchannels,
前記微小流路中に流体の流れが淀む構造を備える気泡捕獲部と、A bubble capture unit having a structure in which a fluid flow is contained in the microchannel;
前記気泡捕獲部近傍に、前記微小流路中に析出した気泡を除去して脱気する脱気手段とを備え、In the vicinity of the bubble capture unit, comprising a deaeration means for degassing by removing the bubbles deposited in the microchannel,
前記気泡捕獲部は、蛇行した構造であることを特徴とするマイクロ流体装置。The microfluidic device, wherein the bubble capturing unit has a meandering structure. 前記脱気手段は、前記微小流路近傍に備えた減圧式脱気流路であることを特徴とする請求項１または２に記載のマイクロ流体装置。 3. The microfluidic device according to claim 1, wherein the deaeration means is a decompression type deaeration channel provided near the micro channel. 前記微小流路と前記脱気流路との間に、通気性部材を設けることを特徴とする請求項３に記載のマイクロ流体装置。 The microfluidic device according to claim 3 , wherein a breathable member is provided between the microchannel and the deaeration channel. 前記通気性部材がシリコン系樹脂であることを特徴とする請求項４に記載のマイクロ流体装置。 The microfluidic device according to claim 4 , wherein the air-permeable member is a silicon-based resin. 前記微小流路と前記減圧式脱気流路との間に、連通する気泡通過用極微細流路を形成することを特徴とする請求項３から５のいずれか一項に記載のマイクロ流体装置。 The microfluidic device according to any one of claims 3 to 5 , wherein an ultrafine channel for passing bubbles is formed between the microchannel and the depressurization type deaeration channel. 前記気泡捕獲部は、角がある構造を備えることを特徴とする請求項１から６のいずれか一項に記載のマイクロ流体装置。 The bubble trap portion, the microfluidic device according to any one of claims 1 6, characterized in that it comprises a certain angular structure.
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