JP6441838B2 - 解析装置及び分離装置 - Google Patents
解析装置及び分離装置 Download PDFInfo
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Description
本実施形態の説明の前に、誘電泳動の概要について説明する。細菌や細胞等の誘電体粒子を含む試料液に対して電極を配置し、電極に周波数ωの交流電圧を供給した場合、試料液中の誘電体粒子に誘電泳動力が作用する。この誘電泳動力FDEPは、次式で表される。
FDEP=2πr3εmRe[K(ω)]∇E2 …(1)
K(ω)=(εp *−εm *)/(εp *+2εm *) …(2)
1.構成
以下の説明では、血液中に含まれる癌細胞を分離する装置を説明する。
以下、実施形態1の分離装置を説明する。図2は、実施形態1に係る分離装置100の構成を示す図である。図2に示す分離装置100は、血中循環癌細胞(CTC)1を含む試料液が所定方向(液流方向)に流れる流路(第1流路)5と、置換部10と、解析部20と、分離部30とを備える。なお、置換部10と解析部20とは、解析装置200を構成する。
置換部10は、血液(懸濁液)における赤血球等の小型細胞2、及び溶液を、DEP液(誘電泳動液)に置換すると共に、血液に含まれる癌細胞1および白血球等の所望のサイズ以上の細胞のみを抽出する。置換部10は、主流路(第2流路)11と、複数の分岐流路12と、廃液チャンバ13とを備え、主流路11と分岐流路12の流路幅、流路高、流路長を変えることで所望のサイズ以上の細胞のみを流路5に導入することができる。
解析部20は、流路5を流れる試料液中の癌細胞1および白血球等の細胞に対する誘電泳動力のクロスオーバー周波数を解析する。解析部20は、一対の電極(第1電極)22、23と、電源部(第1電源部)24と、撮影部25と、制御部(解析部)26とを備える。
分離部30は、流路5において解析部20の後段に設けられ、解析部20で解析された癌細胞1および白血球等の細胞のクロスオーバー周波数に基づいて当該癌細胞1を分離する。分離部30は、一対の電極(第2電極)32、33と、電源部(第2電源部)34と、収集部6、7とを備える。
以下、分離装置100の動作を説明する。図2に示すように、分離装置100は、置換部10において、血液における赤血球等の細胞2及び溶液を、DEP液に置換すると共に、血液に含まれる癌細胞1および白血球等の所望のサイズ以上の細胞のみを抽出する。解析部20は、抽出された癌細胞1および白血球等の細胞に対する誘電泳動力のクロスオーバー周波数を解析する。分離部30は、解析部20で解析された癌細胞1および白血球等の細胞のクロスオーバー周波数に基づいて当該癌細胞1を分離する。以下、分離装置100の動作を詳細に説明する。
以下、解析部20におけるクロスオーバー周波数の解析処理について説明する。図4は、一対の電極22、23の間における癌細胞1の移動軌跡の一例を示す図である。以下では、癌細胞1のクロスオーバー周波数解析処理について説明するが、癌細胞1以外の白血球等の細胞のクロスオーバー周波数解析処理も以下と同様である。図4において、軌跡P1、P2、P3、P4は、図3における時刻t1、t2、t3、t4における癌細胞1の位置である。図3及び図4に示すように、電極22、23間に印加される交流電圧の周波数がクロスオーバー周波数COFよりも低いとき、負の誘電泳動力(斥力)が癌細胞1に作用し、癌細胞1は電極22、23に対して反発して、電極22、23から離れながら流路5を流れる(例えば、区間T1、T3)。一方、電極22、23間に印加される交流電圧の周波数がクロスオーバー周波数COFよりも高いとき、正の誘電泳動力(引力)が癌細胞1に作用し、癌細胞1は電極22、23に引きつけられながら流路5を流れる(例えば、区間T2)。
以上のように、置換部10と解析部20は解析装置200を構成する。本実施形態に係る解析装置200は、血中循環癌細胞(誘電体粒子)1および白血球等の細胞に対する誘電泳動力が斥力から引力に又は引力から斥力に切り替わるクロスオーバー周波数を解析する解析装置であって、流路(第1流路)5と、一対の電極(第1電極)22、23と、電源部(第1電源部)24と、撮影部25と、制御部(解析部)26とを備える。流路5は、誘電泳動液中に癌細胞1および白血球等の細胞を含む試料液が流れる。一対の電極22、23は流路5に配置され、電源部24は、一対の電極22、23に、周波数変調された交流電圧を印加する。撮影部25は、流路5における一対の電極22、23間を流れる癌細胞1および白血球等の細胞の移動軌跡を撮影する。制御部26は、移動軌跡を撮影した画像に基づいて、癌細胞1および白血球等の細胞のクロスオーバー周波数を求める。
上記した実施形態において、本システムの検査対象として細菌や細胞を例示した。本システムの検査対象は、細菌や細胞に限らず、誘電体粒子であればよく、例えば微生物や、真菌、芽胞、ウイルスであってもよい。
2 白血球、赤血球等の細胞
5 流路(第1流路)
6、7 収集部
10 置換部
11 主流路(第2流路)
12 分岐流路
13 廃液チャンバ
20 解析部
22、23 一対の電極(第1電極)
24 電源部(第1電源部)
25 撮影部
26 制御部(解析部、制御部)
30 分離部
32、33 一対の電極(第2電極)
34 電源部(第2電源部)
100 分離装置
200 解析装置
Claims (3)
- 誘電体粒子に対する誘電泳動力が斥力から引力に又は引力から斥力に切り替わるクロスオーバー周波数を解析する解析装置であって、
誘電泳動液中に前記誘電体粒子を含む試料液が流れる第1流路と、
前記第1流路に配置された一対の第1電極と、
前記一対の第1電極に、周波数変調された交流電圧を印加する第1電源部と、
前記第1流路における前記一対の第1電極間を流れる前記誘電体粒子の移動軌跡を撮影する撮影部と、
前記移動軌跡を撮影した画像に基づいて、前記誘電体粒子のクロスオーバー周波数を求める解析部と、
を備える解析装置。 - 前記第1流路の前段に配置され、前記誘電体粒子を含む懸濁液と前記誘電泳動液とが導入される第2流路と、前記第2流路から分岐する分岐流路とを有し、前記懸濁液における溶液を前記分岐流路に分岐させることにより、前記懸濁液における溶液を前記誘電泳動液に置換して前記試料液を生成する置換部をさらに備え、
前記置換部は、前記試料液における前記誘電体粒子を個々に順次に前記第2流路から前記第1流路へ導出する、
請求項1に記載の解析装置。 - 誘電体粒子の分離を行う分離装置であって、
前記請求項1又は2に記載の解析装置と、
前記解析装置の前記第1流路における前記一対の第1電極の後段に配置された一対の第2電極と、
前記一対の第2電極に、所定周波数の交流電圧を印加する第2電源部と、
前記解析装置で解析された誘電体粒子が前記第1流路における一対の第2電極を通過するときに、当該誘電体粒子が誘電泳動を起こすように、前記所定周波数を、当該誘電体粒子に対して前記解析装置で求められたクロスオーバー周波数に基づいて制御する制御部と、
を備える分離装置。
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JP2016016119A JP6441838B2 (ja) | 2016-01-29 | 2016-01-29 | 解析装置及び分離装置 |
CN201780008886.6A CN108603852B (zh) | 2016-01-29 | 2017-01-27 | 解析装置及分离装置 |
EP17744392.6A EP3410107B1 (en) | 2016-01-29 | 2017-01-27 | Analysis device and separation device |
US16/073,770 US10766040B2 (en) | 2016-01-29 | 2017-01-27 | Analysis device and separation device |
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KR102244778B1 (ko) * | 2018-08-31 | 2021-04-27 | 연세대학교 원주산학협력단 | 유전영동힘에 반응하는 세포의 위치변화를 이용한 세포의 교차주파수 측정방법 |
KR102230602B1 (ko) * | 2018-08-31 | 2021-03-22 | 연세대학교 원주산학협력단 | 유전영동힘에 반응하는 세포의 궤적분석을 통한 세포의 cross-over frequency 측정방법 |
CN112740024A (zh) * | 2018-09-24 | 2021-04-30 | 惠普发展公司,有限责任合伙企业 | 从全血进行粒子分离 |
US11946902B2 (en) * | 2018-10-11 | 2024-04-02 | Hewlett-Packard Development Company, L.P. | Dielectrophoresis separator cross-over frequency measurement systems |
DE102020120425A1 (de) * | 2020-08-03 | 2022-02-03 | Fraunhofer-Gesellschaft zur Förderung der angewandten Forschung eingetragener Verein | Verfahren und fluidisches Mikrosystem zur dielektrophoretischen Manipulierung von suspendierten Partikeln |
JPWO2022113677A1 (ja) * | 2020-11-25 | 2022-06-02 | ||
JP7061412B1 (ja) * | 2021-06-14 | 2022-04-28 | 株式会社Afiテクノロジー | 誘電体粒子推定装置及び誘電体粒子種類推定システム |
JP2023005958A (ja) | 2021-06-30 | 2023-01-18 | 株式会社Screenホールディングス | 流路チップおよび誘電泳動装置 |
JP2023006164A (ja) * | 2021-06-30 | 2023-01-18 | 株式会社Afiテクノロジー | 流路チップ、分離システム、及び、分離方法 |
US20230073786A1 (en) * | 2021-09-03 | 2023-03-09 | Hewlett-Packard Development Company, L.P. | Particle separation |
EP4201526A1 (en) * | 2021-12-22 | 2023-06-28 | Imec VZW | Microfluidic device for sorting particles |
JP2024013994A (ja) * | 2022-07-21 | 2024-02-01 | 株式会社Screenホールディングス | 流路チップ |
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US20040060820A1 (en) * | 2002-10-01 | 2004-04-01 | Bressler Vincent Edward | Characterization of particles by position in an electric field |
US7415807B2 (en) | 2005-08-05 | 2008-08-26 | Owens Corning Intellectual Capital Llc | Structured adhesive system |
US7400452B2 (en) | 2005-10-18 | 2008-07-15 | Lightmaster Systems, Inc. | Method and apparatus for internal frames to improve performance and manufacturability of optical devices including liquid crystal on silicon (LCOS) based kernels |
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EP2042239A1 (en) * | 2007-09-10 | 2009-04-01 | Koninklijke Philips Electronics N.V. | Dielectrophoretic device and method for cell membrane studies |
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US20130292247A1 (en) * | 2012-05-01 | 2013-11-07 | Commissariat A L'energie Atomique Et Aux Ene Alt | Method and microsystem for the determination of clausius-mossotti factors for colloidal particles |
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US10518273B2 (en) | 2014-04-09 | 2019-12-31 | Apocell, Inc. | System and method for determining dielectrophoresis crossover frequencies |
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