JP2014509398A - 磁気フローサイトメトリー装置、磁気フローサイトメトリー装置の製造方法および細胞の磁気検出方法 - Google Patents
磁気フローサイトメトリー装置、磁気フローサイトメトリー装置の製造方法および細胞の磁気検出方法 Download PDFInfo
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Abstract
【選択図】図5
Description
1.細胞サンプルがマイクロ流体流路をポンピングされる速度
2.印加された富化磁界の磁界強度
3.懸濁液中における超常磁性にマーキングされた細胞の濃度、並びに
4.使用されたマーカーの磁気特性
5.細胞懸濁液の組成およびレオロジー特性、すなわちたとえばその流動特性、および
6.マーキングされた細胞の種類およびその細胞表面上のアイソトープ数、従って検出すべき漂遊磁界の強度を決定する細胞当りの常磁性マーカの数、
11 入出口
12 半導体チップ(基板)
13 担体板
15 磁気ガイド片
16 パッケージング材料
17 接点
18 ワイヤボンド
20 磁気抵抗センサ
50 マイクロ流体流路
90 細胞サンプル
この磁気フローサイトメトリー装置の製造方法は、
半導体基板上に磁気抵抗センサを形成する工程、
半導体基板上に富化区間の第2部分を取り付ける工程、
担体上に半導体基板をパッケージング(実装)し、担体上に磁気抵抗センサの電気接続部を引き出す工程、
富化区間の第1部分を形成する工程
を有する(請求項10)。
磁気の細胞検出方法によれば、磁気的にマーキングされた細胞サンプルが本発明による磁気フローサイトメトリー装置に注入される。
本発明の有利な実施態様は次の通りである。
*磁気フローサイトメトリー装置に関して
・富化区間が磁気ガイド片を有する(請求項2)。
・磁気ガイド片が強磁性体である(請求項3)。
・富化区間に沿ってフロー室、特にマイクロ流体流路が形成され、マイクロ流体流路を通って流れる磁気的にマーキングされた細胞サンプルが磁気ガイド片で方向付けられる(請求項4)。
・磁石を備え、この磁石がマイクロ流体流路を通って流れる磁気的にマーキングされた細胞サンプルが流路床面にある磁石の磁界により富化されるように配置される(請求項5)。
・マイクロ流体流路の第1部分及び第2部分並びに磁気抵抗センサが次のように、すなわちマイクロ流体流路を通って流れる磁気的にマーキングされた細胞サンプルが先ずマイクロ流体流路の第1部分を通って富化区間の第1部分上に、ついでマイクロ流体流路の第2部分を通って富化区間の第2部分上およびセンサ上に案内され、マイクロ流体流路の第2部分および富化区間の第2部分は、これらによりそれぞれマイクロ流体流路の第1部分および富化区間の第1部分に対するずれが流動する磁気的にマーキングされた細胞サンプルの富化及び方向付けに関して修正されるように配置されている(請求項6)。
・富化区間の長さが少なくとも15000μmである(請求項7)。
・基板の最大拡がりが18000μm以下である(請求項8)。
・磁気抵抗センサがGMR,TMRまたはAMRセンサである(請求項9)。
*磁気フローサイトメトリー装置の製造方法に関して
・半導体基板のパッケージング(実装)工程は、パッケージング材料からマイクロ流体流路が形成されるように行われる(請求項11)。
・射出成形工程においてマイクロ流体流路が形成される(請求項12)。
・富化区間の第1部分の磁気ガイド片が特に熱蒸着またはスパッタリングにより直接流路床面上に堆積される(請求項13)。
・富化区間の第2部分の磁気ガイド片が特に熱蒸着またはスパッタリングにより直接半導体基板上に堆積される(請求項14)。
1.細胞サンプルがマイクロ流体流路をポンピングされる速度
2.印加された富化磁界の磁界強度
3.懸濁液中における超常磁性にマーキングされた細胞の濃度、並びに
4.使用されたマーカーの磁気特性
5.細胞懸濁液の組成およびレオロジー特性、すなわちたとえばその流動特性、および
6.マーキングされた細胞の種類およびその細胞表面上のアイソトープ数、従って検出すべき漂遊磁界の強度を決定する細胞当りの常磁性マーカの数、
11 入出口
12 半導体チップ(基板)
13 担体板
15 磁気ガイド片
16 パッケージング材料
17 接続部
18 電気接続ワイヤ
20 磁気抵抗センサ
50 マイクロ流体流路
90 細胞サンプル
Claims (15)
- 基板(12)上の磁気抵抗センサ(20)と、富化区間(10)とを備え、富化区間(10)が第1部分と第2部分を有し、第2部分が基板(12)上に配置され、第1部分が基板(12)の隣の担体(13)上に配置され、富化区間(10)が基板(12)の縁部を越えて延びるようにされた磁気フローサイトメトリー装置。
- 富化区間(10)が磁気ガイド片(15)を有する請求項1記載の装置。
- 磁気ガイド片(15)が強磁性体である請求項2記載の装置。
- 富化区間(10)に沿ってフロー室(50)、特にマイクロ流体流路が形成され、マイクロ流体流路(50)を通って流れる磁気的にマーキングされた細胞サンプル(90)が磁気ガイド片(15)で方向付けられる請求項2または3記載の装置。
- 磁石を備え、この磁石がマイクロ流体流路(50)を通って流れる磁気的にマーキングされた細胞サンプル(90)が流路床面にある磁石の磁界により富化されるように配置される請求項1から4の1つに記載の装置。
- マイクロ流体流路(50)の第1部分及び第2部分並びに磁気抵抗センサ(20)が次のように、すなわちマイクロ流体流路(50)を通って流れる磁気的にマーキングされた細胞サンプル(90)が先ずマイクロ流体流路(50)の第1部分を通って富化区間(10)の第1部分上に、ついでマイクロ流体流路(50)の第2部分を通って富化区間(10)の第2部分上およびセンサ(20)上に案内され、マイクロ流体流路(50)の第2部分および富化区間(10)の第2部分は、これらによりそれぞれマイクロ流体流路(50)の第1部分および富化区間(10)の第1部分に対するずれが流動する磁気的にマーキングされた細胞サンプル(90)の富化及び方向付けに関して修正されるように配置されている請求項1から5の1つに記載の装置。
- 富化区間(10)の長さが少なくとも15000μmである請求項1から6の1つに記載の装置。
- 基板(12)の最大拡がりが18000μm以下である請求項1から7の1つに記載の装置。
- 磁気抵抗センサ(20)がGMR,TMRまたはAMRセンサである請求項1から8の1つに記載の装置。
- 以下の工程、すなわち
半導体基板(12)上への磁気抵抗センサ(20)の形成、
半導体基板(12)上への富化区間(10)の第2部分の取り付け、
担体(13)上への半導体基板(12)のパッケージングおよび担体(13)上への磁気抵抗センサ(20)の電気接点(1−7、18,28)の引き出し、
富化区間(10)の第1部分の形成
を有する請求項1から9の1つに記載の装置の製造方法。 - 半導体基板(12)のパッケージング工程が、パッケージング材料(16)からマイクロ流体流路(50)が形成されるように行われる請求項10記載の方法。
- 射出成形工程においてマイクロ流体流路(50)が形成される請求項10または12の1つに記載の方法。
- 富化区間(10)の第1部分の磁気ガイド片(15)が特に熱蒸発またはスパッタリングにより直接流路床面上に堆積される請求項10から13の1つに記載の方法。
- 富化区間の第2部分の磁気ガイド片(15)が特に熱蒸発またはスパッタリングにより直接半導体基板(12)上に堆積される請求項10から13の1つに記載の方法。
- 磁気的にマーキングされた細胞サンプル(90)が請求項1から9の1つに記載の装置に注入される細胞の磁気検出方法。
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CN106461686B (zh) * | 2014-05-20 | 2018-06-12 | 尔利生物有限公司 | 用于磁流式细胞仪的盒、磁流式细胞仪及用于利用这样的盒分析样本的方法 |
CN104774761B (zh) * | 2015-03-04 | 2016-09-14 | 江苏大学 | 微流控芯片内细胞直线运动的磁珠驱动方法与装置 |
Citations (8)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
JP2004503775A (ja) * | 2000-06-14 | 2004-02-05 | ボード・オブ・リージェンツ,ザ・ユニヴァーシティ・オヴ・テキサス・システム | 検体混合物の組み合わせた磁気泳動および誘電泳動の操作のための方法および装置 |
JP2005513485A (ja) * | 2001-12-21 | 2005-05-12 | コーニンクレッカ フィリップス エレクトロニクス エヌ ヴィ | 流体中の磁性粒子密度を測定する磁気抵抗検出装置、システム、及び方法 |
JP2006006166A (ja) * | 2004-06-24 | 2006-01-12 | Univ Of Tokyo | 細胞分離装置、及び細胞分離方法 |
JP2006118890A (ja) * | 2004-10-19 | 2006-05-11 | Tokyo Gas Co Ltd | 粒子計量システム、粒子計量方法、プラント劣化検知システムおよびプラント劣化検知方法 |
JP2007256024A (ja) * | 2006-03-22 | 2007-10-04 | Fujifilm Corp | 標的化合物の検出方法 |
US20080124779A1 (en) * | 2006-10-18 | 2008-05-29 | The Regents Of The University Of California | Microfluidic magnetophoretic device and methods for usig the same |
JP2009501930A (ja) * | 2005-07-21 | 2009-01-22 | コーニンクレッカ フィリップス エレクトロニクス エヌ ヴィ | バイオセンサのためのセンサチップ |
JP2010169701A (ja) * | 2008-05-13 | 2010-08-05 | Sony Corp | マイクロチップ |
Family Cites Families (7)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US20040053290A1 (en) * | 2000-01-11 | 2004-03-18 | Terbrueggen Robert Henry | Devices and methods for biochip multiplexing |
US6623984B1 (en) * | 2000-11-01 | 2003-09-23 | The Cleveland Clinic Foundation | MEMS-based integrated magnetic particle identification system |
US6736978B1 (en) * | 2000-12-13 | 2004-05-18 | Iowa State University Research Foundation, Inc. | Method and apparatus for magnetoresistive monitoring of analytes in flow streams |
DE10136275C1 (de) * | 2001-07-25 | 2002-12-12 | Fraunhofer Ges Forschung | Verfahren und Vorrichtung zur Probentrennung |
WO2008114410A1 (ja) * | 2007-03-20 | 2008-09-25 | Shimadzu Corporation | 全有機体炭素測定装置 |
DE102009012108B4 (de) * | 2009-03-06 | 2015-07-16 | Siemens Aktiengesellschaft | Vorrichtung und Verfahren zur Anreicherung und Erfassung von Zellen in strömenden Medien |
DE102009047801B4 (de) * | 2009-09-30 | 2014-06-12 | Siemens Aktiengesellschaft | Durchflusskammer mit Zellleiteinrichtung |
-
2011
- 2011-02-28 DE DE102011004806A patent/DE102011004806A1/de not_active Withdrawn
-
2012
- 2012-02-22 EP EP12710164.0A patent/EP2641087B1/de not_active Not-in-force
- 2012-02-22 CN CN201280010839.2A patent/CN103403551B/zh not_active Expired - Fee Related
- 2012-02-22 CA CA2828294A patent/CA2828294A1/en not_active Abandoned
- 2012-02-22 WO PCT/EP2012/052977 patent/WO2012116913A1/de active Application Filing
- 2012-02-22 JP JP2013555823A patent/JP5766306B2/ja not_active Expired - Fee Related
- 2012-02-22 US US14/001,996 patent/US20130337497A1/en not_active Abandoned
Patent Citations (8)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
JP2004503775A (ja) * | 2000-06-14 | 2004-02-05 | ボード・オブ・リージェンツ,ザ・ユニヴァーシティ・オヴ・テキサス・システム | 検体混合物の組み合わせた磁気泳動および誘電泳動の操作のための方法および装置 |
JP2005513485A (ja) * | 2001-12-21 | 2005-05-12 | コーニンクレッカ フィリップス エレクトロニクス エヌ ヴィ | 流体中の磁性粒子密度を測定する磁気抵抗検出装置、システム、及び方法 |
JP2006006166A (ja) * | 2004-06-24 | 2006-01-12 | Univ Of Tokyo | 細胞分離装置、及び細胞分離方法 |
JP2006118890A (ja) * | 2004-10-19 | 2006-05-11 | Tokyo Gas Co Ltd | 粒子計量システム、粒子計量方法、プラント劣化検知システムおよびプラント劣化検知方法 |
JP2009501930A (ja) * | 2005-07-21 | 2009-01-22 | コーニンクレッカ フィリップス エレクトロニクス エヌ ヴィ | バイオセンサのためのセンサチップ |
JP2007256024A (ja) * | 2006-03-22 | 2007-10-04 | Fujifilm Corp | 標的化合物の検出方法 |
US20080124779A1 (en) * | 2006-10-18 | 2008-05-29 | The Regents Of The University Of California | Microfluidic magnetophoretic device and methods for usig the same |
JP2010169701A (ja) * | 2008-05-13 | 2010-08-05 | Sony Corp | マイクロチップ |
Non-Patent Citations (1)
Title |
---|
JPN7014002549; Welfeng Shen et al.: 'In situ detection of single micron-sized magnetic beads using magnetic tunnel junction sensors' Applied Physics Letters 86, 2005, 253901 * |
Cited By (3)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
JP2018155719A (ja) * | 2017-03-21 | 2018-10-04 | 株式会社東芝 | 磁気センサ、生体細胞検出装置及び診断装置 |
US10849527B2 (en) | 2017-03-21 | 2020-12-01 | Kabushiki Kaisha Toshiba | Magnetic sensor, biological cell sensing device, and diagnostic device |
US11350840B2 (en) | 2017-03-21 | 2022-06-07 | Kabushiki Kaisha Toshiba | Magnetic sensor, biological cell sensing device, and diagnostic device |
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