JP2010227735A - Microchannel device - Google Patents
Microchannel device Download PDFInfo
- Publication number
- JP2010227735A JP2010227735A JP2009074999A JP2009074999A JP2010227735A JP 2010227735 A JP2010227735 A JP 2010227735A JP 2009074999 A JP2009074999 A JP 2009074999A JP 2009074999 A JP2009074999 A JP 2009074999A JP 2010227735 A JP2010227735 A JP 2010227735A
- Authority
- JP
- Japan
- Prior art keywords
- liquid
- manufacturing
- microparticles
- voltage
- asymmetric
- 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.)
- Pending
Links
Abstract
Description
本発明は、液体中の微小粒子を操作するマイクロ流路デバイス、及びこのデバイスの作製方法、操作方法に関する。 The present invention relates to a microchannel device for manipulating microparticles in a liquid, and a method for manufacturing and operating the device.
マイクロ流路チップは、ガラス・シリコン・プラスチック基板上に、幅と深さが数μm〜1数百μmほどの流路を作製したものである。微小液体の制御や反応制御が容易であるため、DNAチップや電気泳動チップなどに応用され、更に化学・生化学分析のための操作を全てマイクロ流路チップに集積するというマイクロ化学分析システム（μTAS： Micro Total Analysis System）が提案され活発に研究が行われている。このような技術は、特許文献としても数多く挙げられるが、例えば特許文献１や特許文献２である。特許文献１ではマイクロ流路構造を工夫し、検査液の溶解・混合処理の精度を向上するとしている。また特許文献２ではマイクロリアクタシステムについて記載されている。 The micro-channel chip is formed by forming a channel having a width and a depth of several μm to several hundred μm on a glass / silicon / plastic substrate. The microchemical analysis system (μTAS) is easy to control microfluids and reactions, so it is applied to DNA chips and electrophoresis chips, and all the operations for chemical and biochemical analysis are integrated in the microchannel chip. : Micro Total Analysis System) has been proposed and actively researched. There are many such techniques as patent documents, for example, Patent Document 1 and Patent Document 2. In Patent Document 1, the micro-channel structure is devised to improve the accuracy of the test solution dissolution / mixing process. Patent Document 2 describes a microreactor system.
現在、細胞・タンパク質などの機能解析や医療用薬品・化学薬品の開発・製造のために、マイクロ流路チップを用いた細胞分析システムの構築が盛んに研究されている。通常の細胞培養実験方法では細胞や培地を必要以上に消費し、更に操作は通常ピペットなどを用い行われるため、操作時間も長くなる。マイクロ流路チップを用いると、分析に必要となる細胞や培地、試薬等も微量ですみ、かつチップ中流体の操作が容易であるため、実験分析が簡便となる。ただ現在のマイクロ流路チップを用いた細胞分析システムは、チップ中の流路と流体に外部から印加した圧力で制御するため、マイクロ流路チップ中の細胞分離・輸送の自由度は低い。また特許文献３ではマイクロ流路チップの開口部より電圧印加し、電気泳動により細胞操作するとしているが、チップ開口部からの電圧印加なので高い電圧が必要であり、また電圧印加方法など流路構造ごとに設計する必要がある。誘電泳動力は、液体中に細胞などの微小粒子があるとき、これに交流電圧を加えると、周波数と電界の勾配に応じて微小粒子は力を受ける。この誘電泳動力の文献として、例えばレビューとして、非特許文献１がある。誘電泳動力を用いた非対称電極による微小粒子の制御方法として、非特許文献２に示されるクリスマスツリー型電極を用いたものがあるが、独立した２つの電極を用い、物理的形状によるブラウン運動の非対称性を利用したものであり、確率論的な制御方法であり不確実なものである。本発明は、独立した複数の非対称電極を用い、マイクロ流路チップ中の細胞分離・輸送を行うものである。 Currently, for the functional analysis of cells and proteins, and the development and production of medical drugs and chemicals, the construction of a cell analysis system using a microchannel chip is being actively studied. In a normal cell culture experiment method, cells and a medium are consumed more than necessary, and the operation is usually performed using a pipette or the like. When a microchannel chip is used, only a very small amount of cells, culture medium, reagents, etc. are required for analysis, and the operation of the fluid in the chip is easy. However, since the current cell analysis system using a microchannel chip is controlled by the pressure applied from the outside to the channel and fluid in the chip, the degree of freedom of cell separation and transport in the microchannel chip is low. In Patent Document 3, a voltage is applied from the opening of the microchannel chip and the cell is operated by electrophoresis. However, since a voltage is applied from the chip opening, a high voltage is required, and a channel structure such as a voltage application method is used. Every design needs to be designed. As for the dielectrophoretic force, when microparticles such as cells are present in a liquid, when an alternating voltage is applied thereto, the microparticles receive a force according to the frequency and the gradient of the electric field. As a document of this dielectrophoretic force, for example, there is Non-Patent Document 1 as a review. As a method of controlling fine particles by an asymmetric electrode using dielectrophoretic force, there is a method using a Christmas tree type electrode shown in Non-Patent Document 2, but using two independent electrodes, the Brownian motion by physical shape is used. It uses asymmetry, is a probabilistic control method, and is uncertain. The present invention uses a plurality of independent asymmetric electrodes to separate and transport cells in a microchannel chip.
マイクロ流路に導入した微小粒子を含む液体で、微小粒子の分離・輸送を行う。 A liquid containing microparticles introduced into a microchannel, which separates and transports microparticles.
本発明によれば、非対称電極をアレイ状に配置し、これに順次交流電圧を印加し、液体中の微小粒子の分離・輸送を行う。特に非対称電極を対にし、相対する電極に位相を１８０°ずらして交流電圧を印加し、相対する電極間に非対称な電界分布をつくることで、微小粒子の分離・輸送を行う。 According to the present invention, asymmetric electrodes are arranged in an array, and an alternating voltage is sequentially applied to the asymmetric electrodes to separate and transport microparticles in the liquid. In particular, asymmetrical electrodes are paired, an alternating voltage is applied to the opposite electrodes by shifting the phase by 180 °, and an asymmetric electric field distribution is created between the opposite electrodes, thereby separating and transporting microparticles.
前記課題を解決するために、本発明のマイクロ流路デバイスは、
基板上に作製した微細液体流路中に非対称電極をアレイ状にならべ、これに電圧を印加することで流路液体中の微小粒子を操作することを特徴としている。
In order to solve the above-mentioned problem, the microchannel device of the present invention includes:
It is characterized in that asymmetrical electrodes are arranged in an array in a fine liquid flow path produced on a substrate, and minute particles in the flow path liquid are manipulated by applying a voltage thereto.
本発明のマイクロ流路デバイスは、
非対称電極のアレイに順次電圧印加を行い、液体中の微小粒子を連続的に操作することを特徴としている。
The microchannel device of the present invention is
A feature is that voltage is sequentially applied to an array of asymmetric electrodes to continuously manipulate fine particles in a liquid.
本発明のマイクロ流路デバイスは、
非対称電極を対にし、対向した電極に位相を１８０°ずらした交流電圧を印加し、液体中の微小粒子を連続的に操作することを特徴としている。
The microchannel device of the present invention is
It is characterized in that an asymmetrical electrode is paired, an alternating voltage having a phase shifted by 180 ° is applied to the opposing electrode, and minute particles in the liquid are continuously operated.
本発明のマイクロ流路デバイスは、
非対称電極対をアレイ状にならべ、非対称電極対に順次電圧印加を行うことで、液体中の微小粒子を連続的に操作することを特徴としている。
The microchannel device of the present invention is
It is characterized in that the asymmetric electrode pairs are arranged in an array and a voltage is sequentially applied to the asymmetric electrode pairs to continuously manipulate the fine particles in the liquid.
本発明のマイクロ流路デバイスは、
非対称電極のアレイに複数の周波数の違う交流電圧を印加し、液体中の微小粒子を操作することを特徴としている。
The microchannel device of the present invention is
It is characterized by manipulating minute particles in a liquid by applying an alternating voltage having a plurality of different frequencies to an array of asymmetric electrodes.
本発明のマイクロ流路デバイスは、
液体中の微小粒子が細胞であることを特徴としている。
The microchannel device of the present invention is
It is characterized in that the fine particles in the liquid are cells.
本発明のマイクロ流路デバイスは、
流路中の液体が血液であることを特徴としている。
The microchannel device of the present invention is
The liquid in the flow path is blood.
本発明のマイクロ流路デバイスは、
非対称電極への電圧印加を、同一基板上に作製した半導体素子を用いて制御することを特徴としている。
The microchannel device of the present invention is
It is characterized in that voltage application to the asymmetric electrode is controlled using a semiconductor element manufactured on the same substrate.
本発明のマイクロ流路デバイスは、
半導体素子がトランジスタであることを特徴としている。
The microchannel device of the present invention is
The semiconductor element is a transistor.
本発明のマイクロ流路デバイスは、
半導体素子が薄膜トランジスタであることを特徴としている。
The microchannel device of the present invention is
The semiconductor element is a thin film transistor.
本発明によれば、マイクロ流路中の微小粒子の分離・移動を局所的・連続的に行うことができ、マイクロ流路チップを用いた細胞分析システムでの応用ではチップ中の特定の細胞の分離・移動が可能となる。 According to the present invention, separation and movement of microparticles in a microchannel can be performed locally and continuously. For application in a cell analysis system using a microchannel chip, specific cells in the chip can be separated. Separation and movement are possible.
本発明に係るマイクロ流路デバイスを実施するための形態を実施例に基づいて以下に説明する。 EMBODIMENT OF THE INVENTION The form for implementing the microchannel device based on this invention is demonstrated below based on an Example.
図１は本発明の実施例によるマイクロ流路チップの概略を説明する図である。図１を参照すると、まず基板上に電極を形成する。電極は例えばチタンと白金の多層膜で作製されている。これにマイクロ流路を形成したPDMS(Polydimethylsiloxane)を張り合わせマイクロ流路チップとする。マイクロ流路中には非対称な形状をした電極が露出している。この非対称な形状により電界分布を形成し、電極に順次電圧印加を行うことにより、微小粒子の移動を行う。図２は本発明の実施例によるマイクロ流路チップ作製工程の例である。図３は本発明の実施例による非対称電極での電界分布の例である。左から2つめの電極対に電圧を印加している。電極が非対称であるため、電位分布も非対称である。図４は本発明の実施例による交流電圧印加方法を説明するための図である。図５は非対称電極を用いた微小粒子の移動操作を行った実施例の写真である。図６はマイクロ流路チップに制御用半導体素子を用いた例を説明するための図である。 FIG. 1 is a diagram for explaining the outline of a microchannel chip according to an embodiment of the present invention. Referring to FIG. 1, an electrode is first formed on a substrate. The electrode is made of, for example, a multilayer film of titanium and platinum. PDMS (Polydimethylsiloxane) having a microchannel formed thereon is bonded to form a microchannel chip. An asymmetrical electrode is exposed in the microchannel. The electric field distribution is formed by this asymmetric shape, and voltage is sequentially applied to the electrodes to move the fine particles. FIG. 2 is an example of a micro-channel chip manufacturing process according to an embodiment of the present invention. FIG. 3 is an example of an electric field distribution at an asymmetric electrode according to an embodiment of the present invention. A voltage is applied to the second electrode pair from the left. Since the electrodes are asymmetric, the potential distribution is also asymmetric. FIG. 4 is a diagram for explaining an AC voltage application method according to an embodiment of the present invention. FIG. 5 is a photograph of an example in which an operation of moving microparticles using an asymmetric electrode was performed. FIG. 6 is a diagram for explaining an example in which a control semiconductor element is used in a microchannel chip.
本発明に係るマイクロ流路デバイスは、例えば微小粒子を含む液体で、微小粒子の分離・輸送に適用して好適なものである。 The microchannel device according to the present invention is, for example, a liquid containing microparticles and is suitable for application to separation / transport of microparticles.
１ 基板
２ 電極パッド
３ PDMS
４ マイクロ流路
５ 金属配線
６ 非対称電極
７ 半導体素子
1 Substrate 2 Electrode pad 3 PDMS
4 Micro-channel 5 Metal wiring 6 Asymmetric electrode 7 Semiconductor element
Claims (10)
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP2009074999A JP2010227735A (en) | 2009-03-25 | 2009-03-25 | Microchannel device |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP2009074999A JP2010227735A (en) | 2009-03-25 | 2009-03-25 | Microchannel device |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| JP2010227735A true JP2010227735A (en) | 2010-10-14 |
Family
ID=43044133
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP2009074999A Pending JP2010227735A (en) | 2009-03-25 | 2009-03-25 | Microchannel device |
Country Status (1)
| Country | Link |
|---|---|
| JP (1) | JP2010227735A (en) |
Cited By (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2015125920A1 (en) * | 2014-02-20 | 2015-08-27 | 国立大学法人大阪大学 | Electrodes for biomolecular sequencing device, and biomolecular sequencing device, method, and program |
| US9535033B2 (en) | 2012-08-17 | 2017-01-03 | Quantum Biosystems Inc. | Sample analysis method |
| US9644236B2 (en) | 2013-09-18 | 2017-05-09 | Quantum Biosystems Inc. | Biomolecule sequencing devices, systems and methods |
| US10202644B2 (en) | 2010-03-03 | 2019-02-12 | Quantum Biosystems Inc. | Method and device for identifying nucleotide, and method and device for determining nucleotide sequence of polynucleotide |
| US10261066B2 (en) | 2013-10-16 | 2019-04-16 | Quantum Biosystems Inc. | Nano-gap electrode pair and method of manufacturing same |
| US10438811B1 (en) | 2014-04-15 | 2019-10-08 | Quantum Biosystems Inc. | Methods for forming nano-gap electrodes for use in nanosensors |
-
2009
- 2009-03-25 JP JP2009074999A patent/JP2010227735A/en active Pending
Cited By (9)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US10202644B2 (en) | 2010-03-03 | 2019-02-12 | Quantum Biosystems Inc. | Method and device for identifying nucleotide, and method and device for determining nucleotide sequence of polynucleotide |
| US10876159B2 (en) | 2010-03-03 | 2020-12-29 | Quantum Biosystems Inc. | Method and device for identifying nucleotide, and method and device for determining nucleotide sequence of polynucleotide |
| US9535033B2 (en) | 2012-08-17 | 2017-01-03 | Quantum Biosystems Inc. | Sample analysis method |
| US9644236B2 (en) | 2013-09-18 | 2017-05-09 | Quantum Biosystems Inc. | Biomolecule sequencing devices, systems and methods |
| US10557167B2 (en) | 2013-09-18 | 2020-02-11 | Quantum Biosystems Inc. | Biomolecule sequencing devices, systems and methods |
| US10261066B2 (en) | 2013-10-16 | 2019-04-16 | Quantum Biosystems Inc. | Nano-gap electrode pair and method of manufacturing same |
| US10466228B2 (en) | 2013-10-16 | 2019-11-05 | Quantum Biosystems Inc. | Nano-gap electrode pair and method of manufacturing same |
| WO2015125920A1 (en) * | 2014-02-20 | 2015-08-27 | 国立大学法人大阪大学 | Electrodes for biomolecular sequencing device, and biomolecular sequencing device, method, and program |
| US10438811B1 (en) | 2014-04-15 | 2019-10-08 | Quantum Biosystems Inc. | Methods for forming nano-gap electrodes for use in nanosensors |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| Zhang et al. | Tunable particle separation in a hybrid dielectrophoresis (DEP)-inertial microfluidic device | |
| Barrett et al. | Dielectrophoretic manipulation of particles and cells using insulating ridges in faceted prism microchannels | |
| Zagnoni et al. | Electrocoalescence mechanisms of microdroplets using localized electric fields in microfluidic channels | |
| Choi et al. | Digital microfluidics | |
| KR101020720B1 (en) | Methods and apparatus for manipulating droplets by electrowetting-based techniques | |
| Saias et al. | Design, modeling and characterization of microfluidic architectures for high flow rate, small footprint microfluidic systems | |
| EP2621631B1 (en) | Microfluidic device for production and collection of droplets of a fluid | |
| Sim et al. | Multistage-multiorifice flow fractionation (MS-MOFF): continuous size-based separation of microspheres using multiple series of contraction/expansion microchannels | |
| Doonan et al. | K-channel: A multifunctional architecture for dynamically reconfigurable sample processing in droplet microfluidics | |
| JP2010227735A (en) | Microchannel device | |
| Rui et al. | Applications of electrowetting-on-dielectric (EWOD) technology for droplet digital PCR | |
| Kaler et al. | Liquid dielectrophoresis and surface microfluidics | |
| Simon et al. | Microfluidic droplet manipulations and their applications | |
| Zhao et al. | Manipulation and separation of oil droplets by using asymmetric nano-orifice induced DC dielectrophoretic method | |
| Shoji et al. | Flow control methods and devices in micrometer scale channels | |
| Chen et al. | Applications and theory of electrokinetic enrichment in micro-nanofluidic chips | |
| Zhou et al. | Droplet fusion by the interplay of electric potential and converging–diverging geometry in micro‐channels | |
| Fouillet et al. | Ewod digital microfluidics for lab on a chip | |
| Sabbagh et al. | Microvalve-Based Tunability of Electrically Driven Ion Transport through a Microfluidic System with an Ion-Exchange Membrane | |
| Malic et al. | Current state of intellectual property in microfluidic nucleic acid analysis | |
| Mukherjee et al. | Plasma separation from blood: The'lab-on-a-chip'approach | |
| Zhang et al. | Microdroplet operations in polymeric microtubes | |
| Lebrasseur et al. | Two-dimensional electrostatic actuation of droplets using a single electrode panel and development of disposable plastic film card | |
| CN110918141B (en) | Microfluidic chip, device containing microfluidic chip and application for preparing micro-emulsified liquid drops | |
| Pei | Optofluidic Devices for Droplet and Cell Manipulation |