JP6721194B2 - デジタルリアルタイムpcr用のカートリッジ - Google Patents
デジタルリアルタイムpcr用のカートリッジ Download PDFInfo
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- JP6721194B2 JP6721194B2 JP2019071938A JP2019071938A JP6721194B2 JP 6721194 B2 JP6721194 B2 JP 6721194B2 JP 2019071938 A JP2019071938 A JP 2019071938A JP 2019071938 A JP2019071938 A JP 2019071938A JP 6721194 B2 JP6721194 B2 JP 6721194B2
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- cartridge
- time pcr
- pcr
- microfluidic chamber
- well array
- Prior art date
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Description
また、試料が反応空間のコーナーやエッジ領域にまで注入されないため、反応空間のコーナーやエッジ領域にエアポケットが生じ得る。エアポケットは、PCR過程中の温度変化によって膨脹または収縮し、試験結果に誤りを発生させる。
一実施例において、デジタルリアルタイムPCR用のカートリッジは、前記微小流体チャンバに付着され、前記微小流体チャンバに形成されたマイクロ流路の底を形成するステッカーをさらに含み得る。
一実施例において、前記CMOSイメージセンサの上部面には、密封後にウェルの底を形成するために薄い層がコーティングされ得る。
一実施例において、前記ウェルアレイは、プラズマまたは熱またはUV硬化接着剤によって前記微小流体チャンバに付着され得る。
一実施例において、前記ウェルアレイにはマイクロウェルが形成され、前記マイクロウェルのピッチは150μm未満であり得る。
一実施例において、前記ウィンドウ部材は、PDMS材質を含み得る。
第1、第2等の用語は、多様な構成要素を説明するために使用することができるが、構成要素は用語によって限定されない。用語は一つの構成要素を他の構成要素から区別する目的としてのみ使用される。例えば、本発明の権利範囲から外れることなく、第1構成要素は第2構成要素と称され、同様に第2構成要素も第1構成要素と称され得る。単数の表現は、文脈上、明白に異ならせて表現しない限り、複数の表現を含む。
図2〜図7を参照すれば、本発明の一実施例によるPCRモジュールは、微小流体チャンバ130、ウェルアレイ140、CMOSフォトセンサアレイ150及びPCB150を含む。
図8を参照すれば、PCR過程の第1段階として、空き状態のPCRモジュールを扁平な位置に配置する。
図9を参照すれば、PCR過程の第2段階として、液体試料を微小流体チャンバ130のインレット134dにピペッティングする。インレット134dにピペッティングされる液体試料の量は、ウェルアレイ140と微小流体チャンバ130との間の空間及びウェルアレイ140のマイクロウェル142に満たされ得る量であることが望ましい。インレット134dにピペッティングされた液体試料は、マイクロ流路134e(図5bに図示)に存在する空気の抵抗によってマイクロ流路134eに流れられない。
図10、図11、図12及び図13を参照すれば、PCR過程の第3段階として、インレット134eに液体試料がピペッティングされた後、通気口152に連結した真空装置(図示せず)をオンする。
図14、図15及び図16を参照すれば、PCR過程の第4段階として、通気口152に連結された真空装置をオフする。前記真空装置がオフされることによって、ウェルアレイ140の下部空間に到達した液体試料は、毛細管の力によってウェルアレイ140の上部空間まで漸進的に引き上げられる。
図17、図18、図19、図20及び図21は、図6に示したPCRモジュールを用いたPCR過程の第5段階を概略的に説明するための断面図である。特に、封止によるPCR過程が図示される。
120 下部ケース
130 微小流体チャンバ
132 ベース部材
134 トップ部材
132a 第1フラット部
132b 支持ホール
132c フラットホール
134a 第2フラット部
134b メンブレインスイッチ
134c インレット部
134d インレット
134e マイクロ流路
134f グリップ部
140 ウェルアレイ
150 CMOSフォトセンサアレイ
152 通気口
160 PCB
170 ヒーター
180 ステッカー
Claims (15)
- 液体試料の投入のために形成されたインレットを含み、射出成形が可能な微小流体チャンバと、
上下部が貫通した複数のマイクロウェルを含み、前記微小流体チャンバの下部面に付着されたウェルアレイと、
前記ウェルアレイの下に配置され、前記ウェルアレイのマイクロウェルに充填された試料の反応映像をリアルタイムで撮影するCMOSフォトセンサアレイと、
前記インレットから液体試料が投入されることによって前記微小流体チャンバに形成されたマイクロ流路、前記ウェルアレイと前記微小流体チャンバと間に形成された空間、及び前記ウェルアレイに形成されたマイクロウェルの真空処理のための通気口が形成されたプリント基板(PCB)と、を含むことを特徴とするデジタルリアルタイムPCR用のカートリッジ。 - 前記微小流体チャンバが、
四角形状の第1フラット部、前記第1フラット部の中心領域に形成された四角形状の支持ホール、前記第1フラット部の角領域に形成された円形状のホールを含む四角形状のベース部材と、
四角形状の第2フラット部、皿形状のメンブレインスイッチ及び閉ループ形状のインレット部を含み、前記ベース部材の上に配置される四角形状のトップ部材を含むことを特徴とする請求項1に記載のデジタルリアルタイムPCR用のカートリッジ。 - 前記微小流体チャンバは、PDMS材質、透明プラスチック、透明ゴム材質のうち少なくとも一つ以上を含むことを特徴とする請求項1に記載のデジタルリアルタイムPCR用のカートリッジ。
- 前記微小流体チャンバに付着され、前記微小流体チャンバに形成されたマイクロ流路の底を形成するステッカーをさらに含むことを特徴とする請求項1に記載のデジタルリアルタイムPCR用のカートリッジ。
- 前記ウェルアレイが、エッチングされたシリコーン材質、金属、セラミック、プラスチック、エポキシ、フォトレジストレジンのうち少なくとも一つ以上を含むことを特徴とする請求項1に記載のデジタルリアルタイムPCR用のカートリッジ。
- 前記CMOSイメージセンサの上部面には、密封後にウェルの底を形成するために薄い層がコーティングされたことを特徴とする請求項1に記載のデジタルリアルタイムPCR用のカートリッジ。
- 前記薄い層が、PDMS材質を含むことを特徴とする請求項6に記載のデジタルリアルタイムPCR用のカートリッジ。
- 前記ウェルアレイが、親水性コーティング処理されたことを特徴とする請求項1に記載のデジタルリアルタイムPCR用のカートリッジ。
- 前記ウェルアレイが、プラズマまたは熱またはUV硬化接着剤によって前記微小流体チャンバに付着されることを特徴とする請求項1に記載のデジタルリアルタイムPCR用のカートリッジ。
- 前記ウェルアレイが、700μm未満の厚さを有することを特徴とする請求項1に記載のデジタルリアルタイムPCR用のカートリッジ。
- 前記ウェルアレイには六角形状のマイクロウェルが形成され、前記マイクロウェルのピッチは150μm未満であることを特徴とする請求項1に記載のデジタルリアルタイムPCR用のカートリッジ。
- 前記微小流体チャンバの上に配置され、上面視で前記インレットの直上に配置されたホールを有する上部ケースと、
前記上部ケースに締結され、前記微小流体チャンバ、前記ウェルアレイ、前記CMOSフォトセンサアレイ及び前記PCBを収容し、上面視で前記通気口の直下に配置されたホールを有する下部ケースと、をさらに含むことを特徴とする請求項1に記載のデジタルリアルタイムPCR用のカートリッジ。 - 前記メンブレインスイッチの上に配置されたウィンドウ部材をさらに含み、
前記ウィンドウ部材は、前記上部ケースの中央領域に形成されたホールに配置されていることを特徴とする請求項12に記載のデジタルリアルタイムPCR用のカートリッジ。 - 前記ウィンドウ部材が、透明な材質を含むことを特徴とする請求項13に記載のデジタルリアルタイムPCR用のカートリッジ。
- 前記ウィンドウ部材が、PDMS材質を含むことを特徴とする請求項13に記載のデジタルリアルタイムPCR用のカートリッジ。
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Family Cites Families (26)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US6261431B1 (en) * | 1998-12-28 | 2001-07-17 | Affymetrix, Inc. | Process for microfabrication of an integrated PCR-CE device and products produced by the same |
ITTO20020808A1 (it) * | 2002-09-17 | 2004-03-18 | St Microelectronics Srl | Dispositivo integrato di analisi del dna. |
AU2005222618A1 (en) * | 2004-03-12 | 2005-09-29 | Biotrove, Inc. | Nanoliter array loading |
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DE102004022263A1 (de) | 2004-05-06 | 2005-12-15 | Clondiag Chip Technologies Gmbh | Vorrichtung und Verfahren zum Nachweis von molekularen Wechselwirkungen |
US7723120B2 (en) | 2005-10-26 | 2010-05-25 | General Electric Company | Optical sensor array system and method for parallel processing of chemical and biochemical information |
US8315817B2 (en) * | 2007-01-26 | 2012-11-20 | Illumina, Inc. | Independently removable nucleic acid sequencing system and method |
US9664619B2 (en) * | 2008-04-28 | 2017-05-30 | President And Fellows Of Harvard College | Microfluidic device for storage and well-defined arrangement of droplets |
US8691509B2 (en) | 2009-04-02 | 2014-04-08 | Fluidigm Corporation | Multi-primer amplification method for barcoding of target nucleic acids |
TW201209159A (en) | 2010-06-17 | 2012-03-01 | Geneasys Pty Ltd | Genetic analysis LOC with non-specific nucleic acid amplification section and subsequent specific amplification of particular sequences in a separate section |
CN101928663B (zh) | 2010-07-23 | 2013-04-17 | 浙江大学 | 用于数字核酸扩增的集成流路芯片装置及应用 |
CN103635802B (zh) * | 2011-04-13 | 2015-10-21 | 阿科尼生物系统公司 | 基于微阵列的样检系统 |
CN102277294B (zh) | 2011-08-03 | 2013-04-17 | 浙江大学 | 一种用于数字核酸扩增的高密度阵列芯片装置 |
US9095852B2 (en) * | 2011-08-22 | 2015-08-04 | The Regents Of The University Of California | Multilayer high density microwells |
EP2856177B1 (en) * | 2012-05-25 | 2020-11-18 | The University of North Carolina At Chapel Hill | Microfluidic devices, solid supports for reagents and related methods |
ITTO20120703A1 (it) * | 2012-08-03 | 2014-02-04 | Biomerieux Sa | Dispositivo microfluidico monouso, cartuccia includente il dispositivo microfluidico, apparecchio per eseguire una amplificazione di acido nucleico, metodo di fabbricazione del dispositivo microfluidico, e metodo di uso del dispositivo microfluidico |
US20160107159A1 (en) | 2013-05-27 | 2016-04-21 | Star Array Pte Ltd | Microfluidic device and method for controlling fluid flow thereinto |
SG11201605013PA (en) * | 2013-11-18 | 2016-07-28 | Life Technologies Corp | Systems and methods for loading liquid samples |
WO2015116627A1 (en) * | 2014-01-29 | 2015-08-06 | Arizona Board Of Regents On Behalf Of Arizona State University | Microreactor array platform |
US10767219B2 (en) | 2014-03-11 | 2020-09-08 | Illumina, Inc. | Disposable, integrated microfluidic cartridge and methods of making and using same |
KR20170016915A (ko) * | 2014-06-11 | 2017-02-14 | 마이크로닉스 인코포레이티드. | 핵산의 분석을 위한 통합 검정 대조군을 갖는 마이크로 유체 공학적 카트리지 및 장치 |
DE102015001998B3 (de) | 2015-02-20 | 2016-02-04 | Friz Biochem Gesellschaft Für Bioanalytik Mbh | Mikrofluidische Kartusche für den Nachweis von Biomolekülen |
JPWO2017061600A1 (ja) * | 2015-10-08 | 2018-08-02 | 凸版印刷株式会社 | マイクロ流体デバイスおよび試料分析方法 |
CN105543064B (zh) | 2015-12-29 | 2018-04-17 | 西安交通大学 | 一种数字pcr芯片及其使用方法 |
CN107262170B (zh) | 2017-07-03 | 2019-04-09 | 重庆大学 | 一种多重数字pcr芯片及其使用方法 |
CN110358681A (zh) | 2019-07-09 | 2019-10-22 | 成都万众壹芯生物科技有限公司 | 一种便携式pcr装置 |
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