JP4753672B2 - 樹脂製マイクロチャネルアレイの製造方法及びこれを用いた血液測定方法 - Google Patents
樹脂製マイクロチャネルアレイの製造方法及びこれを用いた血液測定方法 Download PDFInfo
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- JP4753672B2 JP4753672B2 JP2005270042A JP2005270042A JP4753672B2 JP 4753672 B2 JP4753672 B2 JP 4753672B2 JP 2005270042 A JP2005270042 A JP 2005270042A JP 2005270042 A JP2005270042 A JP 2005270042A JP 4753672 B2 JP4753672 B2 JP 4753672B2
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Images
Classifications
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- B—PERFORMING OPERATIONS; TRANSPORTING
- B81—MICROSTRUCTURAL TECHNOLOGY
- B81C—PROCESSES OR APPARATUS SPECIALLY ADAPTED FOR THE MANUFACTURE OR TREATMENT OF MICROSTRUCTURAL DEVICES OR SYSTEMS
- B81C1/00—Manufacture or treatment of devices or systems in or on a substrate
- B81C1/00015—Manufacture or treatment of devices or systems in or on a substrate for manufacturing microsystems
- B81C1/00023—Manufacture or treatment of devices or systems in or on a substrate for manufacturing microsystems without movable or flexible elements
- B81C1/00055—Grooves
- B81C1/00071—Channels
-
- B—PERFORMING OPERATIONS; TRANSPORTING
- B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
- B01L—CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
- B01L3/00—Containers or dishes for laboratory use, e.g. laboratory glassware; Droppers
- B01L3/50—Containers for the purpose of retaining a material to be analysed, e.g. test tubes
- B01L3/502—Containers for the purpose of retaining a material to be analysed, e.g. test tubes with fluid transport, e.g. in multi-compartment structures
- B01L3/5027—Containers for the purpose of retaining a material to be analysed, e.g. test tubes with fluid transport, e.g. in multi-compartment structures by integrated microfluidic structures, i.e. dimensions of channels and chambers are such that surface tension forces are important, e.g. lab-on-a-chip
- B01L3/502707—Containers for the purpose of retaining a material to be analysed, e.g. test tubes with fluid transport, e.g. in multi-compartment structures by integrated microfluidic structures, i.e. dimensions of channels and chambers are such that surface tension forces are important, e.g. lab-on-a-chip characterised by the manufacture of the container or its components
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- B—PERFORMING OPERATIONS; TRANSPORTING
- B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
- B01L—CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
- B01L2200/00—Solutions for specific problems relating to chemical or physical laboratory apparatus
- B01L2200/12—Specific details about manufacturing devices
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- B—PERFORMING OPERATIONS; TRANSPORTING
- B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
- B01L—CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
- B01L2300/00—Additional constructional details
- B01L2300/08—Geometry, shape and general structure
- B01L2300/0887—Laminated structure
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- Chemical & Material Sciences (AREA)
- Engineering & Computer Science (AREA)
- Health & Medical Sciences (AREA)
- Manufacturing & Machinery (AREA)
- Analytical Chemistry (AREA)
- Microelectronics & Electronic Packaging (AREA)
- Dispersion Chemistry (AREA)
- General Health & Medical Sciences (AREA)
- Hematology (AREA)
- Clinical Laboratory Science (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Investigating Or Analysing Biological Materials (AREA)
- Optical Measuring Cells (AREA)
- Automatic Analysis And Handling Materials Therefor (AREA)
- Investigating Or Analysing Materials By Optical Means (AREA)
Description
(i)基板上への第1レジスト層の形成
(ii)基板とマスクAとの位置合わせ
(iii)マスクAを用いた第1レジスト層の露光
(iv)第1レジスト層の現像、
(v)基板のエッチング、レジスト剥離
(vi)基板上への第2レジスト層の形成
(vii)基板とマスクBとの位置合わせ
(viii)マスクBを用いた第2レジスト層の露光
(ix)レジスト層の現像
(x)基板のエッチング、レジスト剥離
を行い、溝及び窪みに対応するパターンを有する構造体を形成する。
2 第1レジスト層
3 マスクA
4 第2レジスト層
5 マスクB
6 レジストパターン
7 導電性膜
8 金属構造体
9 樹脂製プレート
10 第1の基板
11 流入口
12 流出口
13 窪み
14 壁部
15 微小な溝(微小な流路)
16 平面を有する第2の基板
20 構造体
Claims (18)
- 一端部に形成された流入口と、
他端部に形成された流出口と、
前記流入口が形成される第1の窪みと、
前記流出口が形成される第2の窪みと、
前記第1及び第2の窪みを互いに区画する壁部と、
前記壁部上に形成され、前記第1及び第2の窪みを互いに連通する微小な溝と、を有してなる第1の基板と、
前記第1の基板の表面に接合ないし圧着される平面を有する第2の基板と、を備え、
前記第1の基板と前記第2の基板の接合部ないし圧着部に前記第1及び第2の窪み及び前記溝によって形成される空間を流路として有し、
前記溝の幅、深さがそれぞれ1〜50μmの範囲内であり、かつ、該流路の幅と深さの比が1:10〜10:1の範囲内である樹脂製マイクロチャネルアレイの製造方法であって、
基板をエッチングして、前記窪み及び/又は前記溝に対応するパターンを有する構造体を製造する工程と、
前記構造体に基づいて、前記第1の基板を形成する工程と、を備え、
前記第1の基板を形成する工程において、
前記第1の窪みに、前記流入口を形成する矩形部から前記流出口側に向かって互いに平行に延びた複数の長尺部を設け、
前記第2の窪みに、前記流出口を形成する矩形部から前記流入口側に向かって互いに平行に延びた複数の長尺部を設け、
前記第1の窪みの長尺部と、前記第2の窪みの長尺部とを、交互に配置することを特徴とする樹脂製マイクロチャネルアレイの製造方法。 - 前記基板がガラス又はシリコンにより形成されている請求項1に記載の樹脂製マイクロチャネルアレイの製造方法。
- 一端部に形成された流入口と、
他端部に形成された流出口と、
前記流入口が形成される第1の窪みと、
前記流出口が形成される第2の窪みと、
前記第1及び第2の窪みを互いに区画する壁部と、
前記壁部上に形成され、前記第1及び第2の窪みを互いに連通する微小な溝と、を有してなる第1の基板と、
前記第1の基板の表面に接合ないし圧着される平面を有する第2の基板と、を備え、
前記第1の基板と前記第2の基板の接合部ないし圧着部に前記第1及び第2の窪み及び前記溝によって形成される空間を流路として有し、
前記溝の幅、深さがそれぞれ1〜50μmの範囲内であり、かつ、該流路の幅と深さの比が1:10〜10:1の範囲内である樹脂製マイクロチャネルアレイの製造方法であって、
基板を機械切削して、前記窪み及び/又は前記溝に対応するパターンを有する構造体を製造する工程と、
前記構造体に基づいて、第1の基板を形成工程と、を備え、
前記第1の基板を形成する工程において、
前記第1の窪みに、前記流入口を形成する矩形部から前記流出口側に向かって互いに平行に延びた複数の長尺部を設け、
前記第2の窪みに、前記流出口を形成する矩形部から前記流入口側に向かって互いに平行に延びた複数の長尺部を設け、
前記第1の窪みの長尺部と、前記第2の窪みの長尺部とを、交互に配置することを特徴とする樹脂製マイクロチャネルアレイの製造方法。 - 前記基板上にレジストパターンが形成されており、
前記レジストパターンの形成面から、前記基板及び/又は前記レジストパターンに対して前記エッチング又は前記機械切削が行なわれて、前記構造体が製造される請求項1、2又は3に記載の製造方法。 - 前記構造体に対して、レジストパターンを形成し、
当該レジストパターンの上から金属を付着し、金属構造体を形成する請求項1乃至4のいずれか1項に記載の樹脂製マイクロチャネルアレイの製造方法。 - 前記金属構造体に対して、機械切削又はエッチングを行なうことにより、当該金属構造体を加工する請求項5に記載の樹脂製マイクロチャネルアレイの製造方法。
- 前記構造体又は前記金属構造体を型として、前記樹脂製マイクロチャネルアレイを成形する請求項1乃至6のいずれか1項に記載の樹脂製マイクロチャネルアレイの製造方法。
- 前記構造体又は前記金属構造体に形成されたパターンにしたがって、金属を付着することによって得られた金属構造体を型として前記樹脂製マイクロチャネルアレイを成形する請求項1乃至6のいずれか1項に記載の樹脂製マイクロチャネルアレイの製造方法。
- 前記樹脂製マイクロチャネルアレイに基づいて得られた前記型を用いることを特徴とする請求項7又は8に記載の樹脂製マイクロチャネルアレイの製造方法。
- 請求項1〜9のいずれか1項に記載の製造方法により製造した樹脂製マイクロチャネルアレイを用いた血液測定方法であって、樹脂製マイクロチャネルアレイの単一、又は複数の流入口から、個別、又は同時に生理食塩水、血液試料、試薬を流し、更に測定装置側の流入口近傍及び/又は流出口近傍に流量の制御系を有することにより、各種血液測定に最適な状態を繰り返し再現することを特徴とする血液測定方法。
- 流路によって連通される窪みの流入口、流出口、又は流路部に光を照射する光学系と、該流路から反射、又は透過される光の変量を測定する計測系を有する請求項10記載の血液測定方法。
- 請求項1〜9のいずれか1項に記載の製造方法により製造した樹脂製マイクロチャネルアレイを用いた血液測定方法において、流路によって連通される窪みの流入口、流出口での血液の各有形成分の数の増減、あるいは血液の各有形成分による溝流路の閉塞状況を測定し、それにより血液の各有形成分の流れ特性あるいは活性度を求めることを特徴とする血液測定方法。
- 請求項1〜9のいずれか1項に記載の製造方法により製造した樹脂製マイクロチャネルアレイを用いた血液測定方法において、流路によって連通される窪みの流入口、流出口の間に生理活性物質の濃度差を設けることにより、流路を介して白血球の移動を起こらしめ、その後の各窪みでの白血球分画の数の増減、あるいは白血球による流路の閉塞状況を測定し、それにより白血球分画の遊走能、粘着能を求めることを特徴とする血液測定方法。
- 生理活性物質に暴露後の血液試料に対して血液測定を行うことを特徴とする請求項10〜13のいずれか1項に記載の血液測定方法。
- 血液測定を、蛍光物質で各血球細胞もしくは液体成分のいずれかを蛍光発色させて行うことを特徴とする請求項10〜14のいずれか1項に記載の血液測定方法。
- 前記第1の基板、又は第2の基板のいずれかに金などの薄膜を堆積させ、流路によって連通される窪みの流入口、流出口、又は流路部の誘電率変化を、表面プラズモン共鳴現象による反射光強度の変化として検出する計測系を有する請求項10記載の血液測定方法。
- 流路によって連通される窪みの流入口、流出口又は流路部に、電気化学的に微弱な電気的変位量を検出するセンサを有し、定量評価を行うために電気的増幅を行う請求項10記載の血液測定方法。
- 流路によって連通される窪みの流入口、流出口又は流路部に、超音波による微弱な周波数変化幅を検出するセンサを有し、定量評価を行うために電気信号への変換、及び増幅部を行う請求項10記載の血液測定方法。
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