JP2005121472A - Micro fluid device - Google Patents

Micro fluid device Download PDF

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JP2005121472A
JP2005121472A JP2003356352A JP2003356352A JP2005121472A JP 2005121472 A JP2005121472 A JP 2005121472A JP 2003356352 A JP2003356352 A JP 2003356352A JP 2003356352 A JP2003356352 A JP 2003356352A JP 2005121472 A JP2005121472 A JP 2005121472A
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cantilever
fluid sample
detection
microfluidic device
flow path
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JP4223918B2 (en
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Koichi Shibata
浩一 柴田
Tatsuya Miyatani
竜也 宮谷
Masataka Araogi
正隆 新荻
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Seiko Instruments Inc
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Seiko Instruments Inc
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Abstract

<P>PROBLEM TO BE SOLVED: To provide a micro fluid device capable of preventing the deformation or vibration of cantilevers by reducing a force applied from a fluid sample to the cantilevers for detecting a specific material in the fluid sample flowing in a passage. <P>SOLUTION: In this micro fluid device, a detection cantilever 104 and a reference cantilever 105 are arranged so that the cantilever length direction becomes parallel to the flow direction 107 of the fluid sample flowing in the passage 106 of the micro fluid device. The force applied to the detection cantilever 104 and the reference cantilever 105 from the fluid sample is reduced by this constitution, to thereby prevent the deformation or vibration of the cantilevers. <P>COPYRIGHT: (C)2005,JPO&NCIPI

Description

本発明は、微小流路に微量な流体試料を流し、流体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 allows a small amount of fluid sample to flow through a microchannel and detects a specific substance in the fluid.

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、マイクロ流体装置内の流路を通る流体試料中の微量な特定物質を検出するために、高精度なマイクロセンシング技術が必要とされている。従来のマイクロセンシング技術としては、たとえば特許文献１に記載されているように、微細領域での高感度測定が可能でシステム自体が微小であることから、カンチレバーセンサーをマイクロ流体装置内の流路を通る流体試料中の特定物質を検出する手段として使用しているものがある。図６は、特許文献１に記載されているマイクロ流体装置の流路とカンチレバーセンサーの関係を示した図であり、カンチレバーセンサー６０１は、カンチレバー支持部６０２、カンチレバー支持部６０２に支持された検出用カンチレバー６０３と参照用カンチレバー６０４で構成されている。６０５はマイクロ流体装置の流路、６０６は流体試料の流れ方向を示す矢印である。このカンチレバーセンサー６０１においては、流路脇にカンチレバー支持部６０２が固定され、前記支持部６０２には流路６０５を通る流体試料の流れ方向６０６に対して、カンチレバーの長さ方向が垂直になるように検出用カンチレバー６０３と参照用カンチレバー６０４が支持されている。検出用カンチレバー６０３の一方の面は、流体試料中の特定物質が吸着するように化学修飾されており、特定物質の化学吸着によって検出用カンチレバー６０３がたわむ。ことのき、検出用カンチレバー６０３は温度など化学吸着以外の要因によってもたわむため、化学修飾されていない参照用カンチレバー６０４とのたわみ量の差を測定することで、化学吸着のみによる検出用カンチレバー６０３のたわみ量を測定し、流体試料中の特定物質を検出することができる。
国際公開第０１／３３２２６号パンフレット 図６ At present, microfluidic devices represented by a microchemical analysis system (μTAS) are attracting attention. In the microfluidic device, high-precision microsensing technology is required to detect a small amount of a specific substance in a fluid sample passing through a flow path in the microfluidic device. As a conventional micro-sensing technology, for example, as described in Patent Document 1, since high-sensitivity measurement in a minute region is possible and the system itself is minute, a cantilever sensor is connected to a flow path in a microfluidic device. Some are used as a means for detecting a specific substance in a fluid sample passing therethrough. FIG. 6 is a diagram showing the relationship between the flow path of the microfluidic device described in Patent Document 1 and a cantilever sensor. The cantilever sensor 601 is for detection supported by a cantilever support portion 602 and a cantilever support portion 602. A cantilever 603 and a reference cantilever 604 are included. Reference numeral 605 denotes a flow path of the microfluidic device, and 606 denotes an arrow indicating the flow direction of the fluid sample. In the cantilever sensor 601, a cantilever support 602 is fixed on the side of the flow path, and the length direction of the cantilever is perpendicular to the flow direction 606 of the fluid sample passing through the flow path 605 on the support 602. A detection cantilever 603 and a reference cantilever 604 are supported. One surface of the detection cantilever 603 is chemically modified so that the specific substance in the fluid sample is adsorbed, and the detection cantilever 603 is bent by the chemical adsorption of the specific substance. Since the detection cantilever 603 bends due to factors other than chemical adsorption, such as temperature, the detection cantilever 603 based only on chemical adsorption is measured by measuring the difference in deflection amount from the reference cantilever 604 not chemically modified. The specific amount in the fluid sample can be detected by measuring the amount of deflection.
International Publication No. 01/33226 Pamphlet Fig. 6

しかしながら、特許文献1記載のマイクロ流体装置では、流路を通る流体試料中の特定物質を検出するカンチレバーセンサーにおいて、カンチレバー支持部を流路脇に固定し、カンチレバーの長さ方向が流体の流れ方向に対して垂直になるよう検出用カンチレバーと参照用カンチレバーが前記支持部に支持されている。このような構成とした場合、カンチレバーが流体試料から力を受ける領域が大きくなり、変形や振動を生じやすくなってしまう。   However, in the microfluidic device described in Patent Document 1, in the cantilever sensor that detects a specific substance in a fluid sample passing through the flow path, the cantilever support is fixed to the side of the flow path, and the length direction of the cantilever is the fluid flow direction. The detection cantilever and the reference cantilever are supported by the support portion so as to be perpendicular to each other. In such a configuration, the area where the cantilever receives a force from the fluid sample increases, and deformation and vibration are likely to occur.

そこで本発明は、流路を通る流体試料中の特定物質を検出するためのカンチレバーが、流体試料から受ける力を減少させ、カンチレバーの変形や振動などを防ぐことができるマイクロ流体装置を提供することを課題とする。   Therefore, the present invention provides a microfluidic device that can reduce the force that a cantilever for detecting a specific substance in a fluid sample passing through a flow path receives from the fluid sample and prevent the cantilever from being deformed or vibrated. Is an issue.

以上のような課題を解決するため、本発明におけるマイクロ流体装置では、マイクロ流体装置の流路内を通る流体試料の流れ方向に対してカンチレバーの長さ方向が平行になるよう、検出用カンチレバーと参照用カンチレバーを配置した。このような配置にすることで、検出用カンチレバーと参照用カンチレバーが流体試料から受ける力を減少させ、カンチレバーの変形や振動などを防ぐことができる。   In order to solve the above problems, in the microfluidic device according to the present invention, the detection cantilever and the detection cantilever are arranged so that the length direction of the cantilever is parallel to the flow direction of the fluid sample passing through the flow path of the microfluidic device. A reference cantilever was placed. With such an arrangement, the force that the detection cantilever and the reference cantilever receive from the fluid sample can be reduced, and deformation or vibration of the cantilever can be prevented.

また、検出用カンチレバーと参照用カンチレバーの自由端の方向を、カンチレバー支持部を挟んで反対方向に支持すると、カンチレバー支持部の幅を流路の幅方向に対して小さくすることができる。   If the direction of the free end of the detection cantilever and the reference cantilever is supported in the opposite direction across the cantilever support, the width of the cantilever support can be reduced relative to the width direction of the flow path.

さらにカンチレバー支持部の厚さを、検出用カンチレバーと参照用カンチレバーの厚さよりも厚くすることで、カンチレバー支持部が流路を通る流体試料から受ける力によって変形、振動することがなくなる。   Furthermore, by making the thickness of the cantilever support portion thicker than the thickness of the detection cantilever and the reference cantilever, the cantilever support portion is not deformed or vibrated by the force received from the fluid sample passing through the flow path.

本発明のマイクロ流体装置は、マイクロ流体装置の流路を通る流体試料の流れ方向に対してカンチレバーの長さ方向が平行になるよう、検出用カンチレバーと参照用カンチレバーを配置することで、検出用カンチレバーと参照用カンチレバーが流体試料から受ける力を減少させ、カンチレバーの変形や振動などを防ぐことができる。したがって本発明のマイクロ流体装置では、流体試料から働く力によってカンチレバーセンサーが外乱を受けず、流体試料中の特定物質との化学反応によってのみ生ずる検出用カンチレバーのたわみを検出の対象とすることができ、測定精度、分解能を向上させることができる。   In the microfluidic device of the present invention, the detection cantilever and the reference cantilever are arranged so that the length direction of the cantilever is parallel to the flow direction of the fluid sample passing through the flow path of the microfluidic device. The force received from the fluid sample by the cantilever and the reference cantilever can be reduced, and deformation or vibration of the cantilever can be prevented. Therefore, in the microfluidic device of the present invention, the cantilever sensor is not disturbed by the force acting from the fluid sample, and the deflection of the detection cantilever that occurs only by a chemical reaction with a specific substance in the fluid sample can be detected. Measurement accuracy and resolution can be improved.

以下、この発明における実施例を、図面を用いて説明する。なお、この実施例により本発明が限定されるものではない。   Embodiments of the present invention will be described below with reference to the drawings. In addition, this invention is not limited by this Example.

図１は、本発明の実施例1におけるマイクロ流体装置の流路と、流路を通る流体試料中の特定物質を検出するカンチレバーセンサーの関係図である。カンチレバーセンサー１０１は、カンチレバーセンサーの基板１０２、基板1０２に固定されたカンチレバー支持部1０３、カンチレバー支持部1０３に支持された検出用カンチレバー１０４と参照用カンチレバー１０５で構成されている。１０６はマイクロ流体装置の流路、1０７は流体試料の流れ方向を示す矢印である。   FIG. 1 is a relationship diagram of a channel of the microfluidic device according to the first embodiment of the present invention and a cantilever sensor that detects a specific substance in a fluid sample passing through the channel. The cantilever sensor 101 includes a cantilever sensor substrate 102, a cantilever support portion 103 fixed to the substrate 102, a detection cantilever 104 supported by the cantilever support portion 103, and a reference cantilever 105. 106 is a flow path of the microfluidic device, and 1007 is an arrow indicating the flow direction of the fluid sample.

図２は、実施例１で使用するカンチレバーセンサー１０１の斜視図であり、カンチレバー支持部１０３は、自身と比べて厚い基板１０２に固定されている。なお、カンチレバー支持部１０３は、検出用カンチレバー１０４および参照用カンチレバーよりも厚さを厚くすることにより、強度を高めることが可能となる。   FIG. 2 is a perspective view of the cantilever sensor 101 used in the first embodiment, and the cantilever support portion 103 is fixed to a substrate 102 that is thicker than itself. The cantilever support portion 103 can be increased in strength by making it thicker than the detection cantilever 104 and the reference cantilever.

また、図５は本発明におけるマイクロ流体装置内のマイクロセル５０１の構成図であって、５０２は流体試料の入力ポート、５０３はマイクロバルブ、５０４は流体試料の出力ポートである。マイクロ流体装置内のマイクロセル５０１においては、入力ポート５０２に供給された流体試料が流路１０６を通り、流体試料の流れ量をマイクロバルブ５０３によって制御し、カンチレバーセンサー１０１が流路１０６を通る流体試料中の特定物質を検出し、測定後の流体試料は出力ポート５０４から排出される構造となっている。検出用カンチレバー１０４は流路１０６を通る流体試料中の特定物質が吸着するように表面に化学修飾がされており、特定物質を吸着することによって検出用カンチレバー１０４がたわむ。一方、参照用カンチレバー１０４には化学修飾がされていない。そして検出用カンチレバー１０４のたわみと参照用カンチレバー１０５のたわみとの差を測定することで、化学吸着のみによる検出用カンチレバー１０４のたわみ量を測定することができ、流体試料内の特定物質を検出することができる。   FIG. 5 is a configuration diagram of the microcell 501 in the microfluidic device according to the present invention, where 502 is a fluid sample input port, 503 is a microvalve, and 504 is a fluid sample output port. In the microcell 501 in the microfluidic device, the fluid sample supplied to the input port 502 passes through the flow path 106, the flow amount of the fluid sample is controlled by the microvalve 503, and the cantilever sensor 101 flows through the flow path 106. A specific substance in the sample is detected, and the measured fluid sample is discharged from the output port 504. The detection cantilever 104 is chemically modified on the surface so that a specific substance in the fluid sample passing through the flow path 106 is adsorbed, and the detection cantilever 104 bends by adsorbing the specific substance. On the other hand, the reference cantilever 104 is not chemically modified. Then, by measuring the difference between the deflection of the detection cantilever 104 and the deflection of the reference cantilever 105, the deflection amount of the detection cantilever 104 only by chemical adsorption can be measured, and a specific substance in the fluid sample is detected. be able to.

再び図１に基づいて説明をおこなう。基板１０２は流路１０６の脇にスペースを設け固定され、基板１０２に固定されたカンチレバー支持部１０３があり、カンチレバー支持部１０３にそれぞれ支持された検出用カンチレバー１０４と参照用カンチレバー１０５は長さ方向が、流路１０６を通る流体試料の流れ方向１０７と平行となり、かつ支持部１０３の同じエッジに自由端の方向が一致するよう取付けられている。検出用カンチレバー１０４と参照用カンチレバー１０５をこのように配置することで、流路１０６を通る流体試料から力を受ける領域を小さくすることができ、カンチレバー１０４、１０５が変形、振動を生じにくくなり、測定精度、分解能が低下することを防ぐことができる。また、カンチレバー支持部１０３の厚さを、検出用カンチレバー１０４と参照用カンチレバー１０５よりも厚くすることで、カンチレバー支持部１０３が流路１０６を通る流体試料から受ける力によって変形、振動することがなく、化学吸着によっても変形しないため、検出用カンチレバー１０４と参照用カンチレバー１０５のたわみ測定に影響を与えない。   The description will be given again with reference to FIG. The substrate 102 is fixed by providing a space beside the flow path 106, and has a cantilever support portion 103 fixed to the substrate 102. The detection cantilever 104 and the reference cantilever 105 respectively supported by the cantilever support portion 103 are arranged in the length direction. Are attached in parallel to the flow direction 107 of the fluid sample passing through the flow path 106, and the direction of the free end coincides with the same edge of the support portion 103. By arranging the detection cantilever 104 and the reference cantilever 105 in this way, the region receiving the force from the fluid sample passing through the flow path 106 can be reduced, and the cantilevers 104 and 105 are less likely to be deformed and vibrated, It is possible to prevent a decrease in measurement accuracy and resolution. Further, by making the thickness of the cantilever support portion 103 thicker than that of the detection cantilever 104 and the reference cantilever 105, the cantilever support portion 103 is not deformed or vibrated by the force received from the fluid sample passing through the flow path 106. Since it is not deformed even by chemical adsorption, it does not affect the deflection measurement of the detection cantilever 104 and the reference cantilever 105.

図３は、本発明の実施例２におけるカンチレバーセンサー２０１の構成図であって、カンチレバーセンサー２０１は流路１０６に対して図４のように設置される。つまり、実施例1においては、検出用カンチレバー２０４と参照用カンチレバー２０５を、支持部２０３の同じエッジに自由端の方向を揃えて配置したが、実施例２では前記カンチレバー支持部２０３に支持された検出用カンチレバー２０４と参照用カンチレバー２０５が、長さ方向がマイクロ流体装置の流路１０６を通る流体試料の流れ方向１０７と平行となり、かつ支持部２０３をはさんで自由端の方向が反対方向になるよう設置した。このような配置にすることで、カンチレバー支持部２０３の幅を流路１０６の幅方向に対して小さくできるため、流路１０６の断面径を小さくし、流路１０６を通る流体試料の量を減少させることが可能となる。さらに、検出用カンチレバー２０４の自由端と固定端を結ぶ直線と、参照用カンチレバー２０５の自由端と固定端を結ぶ直線は同一直線上にあるため、前記マイクロ流体装置の流路１０６を通る流体試料の試料成分が分離して層流となったとしても、同一層の同一成分についての特定物質を検出できる。   FIG. 3 is a configuration diagram of the cantilever sensor 201 according to the second embodiment of the present invention. The cantilever sensor 201 is installed with respect to the flow path 106 as shown in FIG. That is, in the first embodiment, the detection cantilever 204 and the reference cantilever 205 are arranged with the same edge of the support portion 203 aligned in the direction of the free end, but in the second embodiment, the detection cantilever 204 is supported by the cantilever support portion 203. The detection cantilever 204 and the reference cantilever 205 have a length direction parallel to the flow direction 107 of the fluid sample passing through the flow path 106 of the microfluidic device, and the free end direction is opposite to the support portion 203. Was installed. With such an arrangement, the width of the cantilever support portion 203 can be reduced with respect to the width direction of the flow path 106, so that the cross-sectional diameter of the flow path 106 is reduced and the amount of fluid sample passing through the flow path 106 is reduced. It becomes possible to make it. Further, since the straight line connecting the free end and the fixed end of the detection cantilever 204 and the straight line connecting the free end and the fixed end of the reference cantilever 205 are on the same straight line, the fluid sample passing through the channel 106 of the microfluidic device. Even if the sample components are separated into a laminar flow, a specific substance for the same component in the same layer can be detected.

なお、実施例１、２において、検出用カンチレバーと参照用カンチレバーは、少なくとも一本ずつあればよく、検出用カンチレバーと参照用カンチレバーは、必ずしも同数である必要は無い。また、複数の検出用カンチレバー設置し、各検出用カンチレバーに異なる物質を化学吸着させるようにすることで、流路１０６を通る流体試料中の複数の物質を検出できるカンチレバーセンサーを有したマイクロ流体装置を形成することができる。   In the first and second embodiments, at least one detection cantilever and one reference cantilever are sufficient, and the number of detection cantilevers and the reference cantilevers are not necessarily the same. Also, a microfluidic device having a cantilever sensor that can detect a plurality of substances in a fluid sample passing through the flow path 106 by installing a plurality of detection cantilevers and causing each detection cantilever to chemically adsorb different substances. Can be formed.

本発明の実施例１におけるマイクロ流体装置の流路とカンチレバーセンサーの関係図FIG. 3 is a relationship diagram of a flow path and a cantilever sensor of the microfluidic device according to the first embodiment of the present invention. 本発明の実施例１におけるカンチレバーセンサーの構成図1 is a configuration diagram of a cantilever sensor according to Embodiment 1 of the present invention. 本発明の実施例２におけるカンチレバーセンサーの構成図Configuration diagram of a cantilever sensor in Embodiment 2 of the present invention 本発明の実施例２におけるマイクロ流体装置の流路とカンチレバーセンサーの関係図FIG. 5 is a diagram illustrating the relationship between the flow path of the microfluidic device and the cantilever sensor in the second embodiment of the present invention. 本発明の実施例１におけるマイクロ流体装置内のマイクロセルの構成図Configuration diagram of microcell in microfluidic device in Embodiment 1 of the present invention 従来技術におけるカンチレバーセンサーの概略図Schematic diagram of a conventional cantilever sensor

符号の説明Explanation of symbols

１０１、２０１、６０１ カンチレバーセンサー
１０２ カンチレバーチップ基板
１０３、２０３、６０２ カンチレバー支持部
１０４、２０４、６０３ 検出用カンチレバー
１０５、２０５、６０４ 参照用カンチレバー
１０６、６０５ 流路
１０７、６０６ 流体試料の流れ方向
５０１ マイクロ流体装置内のマイクロセル
５０２ 流体試料の入力ポート
５０３ マイクロバルブ
５０４ 流体試料の出力ポート 101, 201, 601 Cantilever sensor 102 Cantilever chip substrate 103, 203, 602 Cantilever support 104, 204, 603 Detection cantilever 105, 205, 604 Reference cantilever 106, 605 Flow path 107, 606 Flow direction of fluid sample 501 Micro Microcell 502 in fluidic device Fluid sample input port 503 Microvalve 504 Fluid sample output port

Claims (5)

流体試料が通る流路を備えた基板と、前記基板に備えられた検出器からなり、該検出器により流体試料中の特定物質を検出するマイクロ流体装置であって、前記検出器は複数のカンチレバーと該複数のカンチレバーを支持するカンチレバー支持部とを備え、該複数のカンチレバーは該カンチレバーの長さ方向がマイクロ流体装置の流路を通る流体試料の流れ方向に対して平行となるように備えられているマイクロ流体装置。   A microfluidic device comprising a substrate having a flow path through which a fluid sample passes and a detector provided on the substrate, wherein the detector detects a specific substance in the fluid sample, the detector comprising a plurality of cantilevers And a cantilever support for supporting the plurality of cantilevers, the plurality of cantilevers being provided such that the length direction of the cantilevers is parallel to the flow direction of the fluid sample passing through the flow path of the microfluidic device. A microfluidic device. 前記複数のカンチレバーは、少なくとも１本の検出用カンチレバーと、少なくとも１本の参照用カンチレバーからなる請求項１に記載のマイクロ流体装置。   The microfluidic device according to claim 1, wherein the plurality of cantilevers include at least one detection cantilever and at least one reference cantilever. 前記複数のカンチレバーのうち、少なくとも一本のカンチレバーの自由端方向が、他のカンチレバーの自由端方向に対して反対方向に支持されてい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 fluid according to claim 1, wherein a free end direction of at least one cantilever among the plurality of cantilevers is supported in a direction opposite to a free end direction of another cantilever. apparatus. 前記検出用カンチレバーの自由端方向が、前記参照用カンチレバーの自由端方向に対して反対方向に支持されたカンチレバーセンサーを備えた、請求項１から３のいずれかに記載のマイクロ流体装置。   4. The microfluidic device according to claim 1, further comprising a cantilever sensor in which a free end direction of the detection cantilever is supported in a direction opposite to a free end direction of the reference cantilever. 前記カンチレバー支持部の厚さが、前記検出用カンチレバーと前記参照用カンチレバーの厚さよりも厚いことを特徴とする、請求項１から４のいずれかに記載のマイクロ流体装置。   5. The microfluidic device according to claim 1, wherein a thickness of the cantilever support portion is greater than a thickness of the detection cantilever and the reference cantilever.
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Cited By (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US20100071477A1 (en) * 2007-02-15 2010-03-25 Georg Haehner Flow Velocity and Pressure Measurement Using a Vibrating Cantilever Device

Cited By (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US20100071477A1 (en) * 2007-02-15 2010-03-25 Georg Haehner Flow Velocity and Pressure Measurement Using a Vibrating Cantilever Device
US8371184B2 (en) * 2007-02-15 2013-02-12 The University Court Of The University Of St. Andrews Flow velocity and pressure measurement using a vibrating cantilever device

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