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CN1997453A - 微流芯片 - Google Patents

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CN1997453A
CN1997453A CNA2004800430697A CN200480043069A CN1997453A CN 1997453 A CN1997453 A CN 1997453A CN A2004800430697 A CNA2004800430697 A CN A2004800430697A CN 200480043069 A CN200480043069 A CN 200480043069A CN 1997453 A CN1997453 A CN 1997453A
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赖纳·格岑
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    • G01MEASURING; TESTING
    • G01NINVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N35/00Automatic analysis not limited to methods or materials provided for in any single one of groups G01N1/00 - G01N33/00; Handling materials therefor
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    • G01N35/085Flow Injection Analysis
    • GPHYSICS
    • G01MEASURING; TESTING
    • G01NINVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N33/00Investigating or analysing materials by specific methods not covered by groups G01N1/00 - G01N31/00
    • G01N33/48Biological material, e.g. blood, urine; Haemocytometers
    • G01N33/50Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing
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    • G01N33/5302Apparatus specially adapted for immunological test procedures
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    • GPHYSICS
    • G01MEASURING; TESTING
    • G01NINVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N35/00Automatic analysis not limited to methods or materials provided for in any single one of groups G01N1/00 - G01N33/00; Handling materials therefor
    • G01N35/00029Automatic analysis not limited to methods or materials provided for in any single one of groups G01N1/00 - G01N33/00; Handling materials therefor provided with flat sample substrates, e.g. slides
    • G01N35/00069Automatic analysis not limited to methods or materials provided for in any single one of groups G01N1/00 - G01N33/00; Handling materials therefor provided with flat sample substrates, e.g. slides whereby the sample substrate is of the bio-disk type, i.e. having the format of an optical disk
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    • B01L2200/10Integrating sample preparation and analysis in single entity, e.g. lab-on-a-chip concept
    • GPHYSICS
    • G01MEASURING; TESTING
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    • G01N2035/00099Characterised by type of test elements
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    • GPHYSICS
    • G01MEASURING; TESTING
    • G01NINVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N35/00Automatic analysis not limited to methods or materials provided for in any single one of groups G01N1/00 - G01N33/00; Handling materials therefor
    • G01N2035/00178Special arrangements of analysers
    • G01N2035/00237Handling microquantities of analyte, e.g. microvalves, capillary networks

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Abstract

本发明涉及用于生物、化学及药物学分析的微流芯片,该芯片中设置有空穴以及使这些空穴相互连接的、由于毛细作用而输送分析及合成所需液体的通道,其中这些空穴的至少一个是反应室,其特征在于根据三维层状模型的光固化亲水性塑料材料的层状结构以及疏水性材料的覆盖层,其中在由亲水性材料构成的层状成型体中来自不同空穴的不交叉的通道通向至少一个反应室中。

Description

微流芯片
技术领域
本发明涉及用于生物、化学及药物学分析及合成的微流芯片,该芯片中设置有空穴以及使这些空穴相互连接的、由于毛细作用而输送分析所需液体的通道,其中这些空穴的至少一个是反应室。
背景技术
微流元件利用毛细作用力、亲水力及疏水力,从而在不使用泵的情况下使液体物质在系统中移动。为此需要分流器及混合器。但目前已有的系统中不可能使两股液体流在流芯片上交叉而不发生混合。
但所述芯片例如必须在反应室中才使待测液体(血液)与分析液体汇合,从而根据待观察的反应对待测物质作出评价。
因此,微流芯片的构成必须使输送流体的通道以及从中输送出液体的空穴完全相互分离。
若该芯片能够以一种可实施后切割的方式制造,,则这可以简单的方式现实。
发明内容
因此,本发明的目的是通过根据三维层状模型的光固化亲水性塑料材料的层状结构以及疏水性材料的覆盖层实现的,其中在由亲水性材料构成的层状成型体中来自不同空穴的不交叉的通道通向至少一个反应室中。
该层状结构是已知的生产技术,其中例如在两个板之间由于其表面张力而保持一种光固化的液体。这些板中的一个是可透过电磁波的。DE-PS 4420996中描述了该方法。
待形成的成型体的模型例如在计算机中同样存储在虚拟的层中,将其逐步取出,通过以逐层的方式将两个板分离并送入新鲜材料而可以形成极薄的层,这可以产生极精确且极小的结构,例如空穴、通道以及通过隔板部分地桥接的空穴。以此方式一方面可以使空穴严格地相互分离,另一方面同样可以使输送不同液体的通道严格地相互分离。
在本发明的一个优选的具体实施方案中,在该芯片中产生一个被疏水性层覆盖的中央空穴,该中央空穴被一个环形空穴包围,该环形空穴具有同样被疏水性层覆盖的由隔板相互分离的开口,从这些开口均经过一个通道通向一个与开口相连的反应室,该反应室与其他反应室一起呈放射形围绕中央空穴及环形空穴排列,而在隔板的表面中从中央空穴经过桥接环形空穴的通道通向每个相连的反应室,其中来自环形空穴以及来自中央空穴的通道转向转向在所述空穴的壁内垂直上升、朝所述空穴的内部空间开口的槽。
在此情况下,所用的产生或分层结构的方法确保通道的边缘在其从水平转向垂直的位置上可以是极尖锐的,从而使亲水性材料的毛细作用非常明显。
根据本发明的另一个具体实施方案,垂直地排列在壁中的通道在其空穴底端与底部表面形成锐角。
在一个具体实施方案中,在该位置上垂直向下的通道从该空穴退回一小段,这同样通过常规成型法是不可能的。但是此类结构对于最优化毛细作用是重要的。
为了进一步最优化毛细作用,通道或空穴被疏水性层覆盖是值得期待的。
根据本发明,以如下方式产生该疏水性层,首先由一层或更多层光固化塑料材料形成薄片,其中最后一层仅部分地聚合。该聚合反应通过用电磁波照射而以已知的方式加以实施。
利用该部分聚合的层将如此形成的薄片覆盖在预先形成的微流芯片上,然后使此时仅部分聚合的层完全聚合,从而获得该芯片的整体结构。
以此方式,能够省略在覆盖时可以添加至细通道的粘结剂等。
为了能够大批量生产所述微流芯片,在至少一个轧辊对之间连续地形成薄片,其中在两个轧辊之间设置有光固化材料,这两个轧辊中的一个具有用于固化的照明设备,并且同样在连续方法中将如此产生的覆盖层覆盖在大批量生产的微流芯片上,并实施完全聚合。
附图说明
附图所示为大比例放大的微流芯片的截面,但其中省略了覆盖层。
具体实施方式
该芯片具有一个中央空穴1,该中央空穴1被环形空穴2包围并通过壁3与该环形空穴2分离。该环形空穴2具有呈放射形排列的开口4,该开口4由隔板5相互分离。
由中央空穴1的底部垂直上升的通道6经过隔板5通向另一个空穴7。该空穴7例如是反应室。
在该室中,从中央空穴1经过通道6送入的液体与例如从环形空穴2经过通道8送入的分析液体反应。通道8从环形空穴2的底部向上升入该空穴的壁内,然后不交叉地从通道6通向空穴7。
液体的输送是通过构成微流芯片的亲水性材料的毛细作用进行的。在此情况下重要的是,一方面未示出的覆盖材料具有疏水性,另一方面通道的边缘在从垂直转向水平的位置上是极尖锐的。这一方面涉及从空穴1和2通向芯片表面的垂直上升的通道6和8的边缘,还涉及各空穴底部上的这些垂直的通道的边缘。在这些位置上,通道嵌入壁中一段,并与底部表面形成一个锐角。
此类芯片例如由制造者用分析液体在环形空间2中填充。利用移液管或注射器将待测材料,例如血液或血液成分,经过未在此示出的覆盖层充入中央空穴1中以进行测试。然后由于毛细作用力,使两种液体流入室7中。根据在那里发生的反应,可以对待测材料作出评价。

Claims (5)

1、用于生物、化学及药物学分析的微流芯片,该芯片中设置有空穴以及使这些空穴相互连接的、由于毛细作用而输送分析及合成所需液体的通道,其中这些空穴的至少一个是反应室,其特征在于根据三维层状模型的光固化亲水性塑料材料的层状结构以及疏水性材料的覆盖层,其中在由亲水性材料构成的层状成型体中来自不同空穴(1、2)的不交叉的通道(6、8)通向至少一个反应室(7)中。
2、根据权利要求1所述的微流芯片,其特征在于,在该芯片中产生一个被疏水性层覆盖的中央空穴(1),该中央空穴(1)被一个环形空穴(2)包围,该环形空穴(2)具有同样被疏水性层覆盖的由隔板(5)相互分离的开口(4),从这些开口均经过一个通道(8)通向一个与开口相连的反应室(7),该反应室(7)与其他反应室一起呈放射形围绕所述中央空穴(1)及所述环形空穴(4)排列,而在所述隔板(5)的表面中从所述中央空穴(1)经过桥接所述环形空穴(2)的通道(6)通向每个相连的反应室(7),其中来自所述环形空穴(2)以及来自所述中央空穴(1)的通道(6、8)转向在所述空穴(1、2)的壁内垂直上升、朝所述空穴(1、2)的内部空间开口的槽。
3、根据权利要求2所述的微流芯片,其特征在于,垂直地排列在所述壁中的通道(6、8)在其空穴底端与底部表面形成锐角。
4、用于制造根据权利要求1至3之一所述的微流芯片的覆盖层的方法,其特征在于,首先由一层或更多层光固化塑料材料形成薄片,其中最后一层仅部分地聚合,然后利用该部分聚合的层将如此形成的薄片覆盖在预先产生的微流芯片上,并使此时仅部分聚合的层完全聚合,从而获得该芯片的整体结构。
5、根据权利要求4所述的方法,其特征在于,在至少一个轧辊对之间连续地形成薄片,其中在两个轧辊之间设置有光固化材料,这两个轧辊中的一个具有用于固化的照明设备,并且同样在连续方法中将如此产生的覆盖层覆盖在大批量生产的微流芯片上,并实施完全聚合。
CNB2004800430697A 2004-03-17 2004-11-17 微流芯片 Expired - Fee Related CN100509165C (zh)

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DE102004013161.9 2004-03-17
DE102004013161A DE102004013161B4 (de) 2004-03-17 2004-03-17 Mikrofluidik-Chip

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EP (1) EP1725330B1 (zh)
JP (1) JP2007529720A (zh)
KR (1) KR20070012799A (zh)
CN (1) CN100509165C (zh)
AT (1) ATE385852T1 (zh)
CA (1) CA2559913C (zh)
DE (2) DE102004013161B4 (zh)
DK (1) DK1725330T3 (zh)
ES (1) ES2303118T3 (zh)
TW (1) TWI295273B (zh)
WO (1) WO2005089944A2 (zh)

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TWI461689B (zh) * 2010-04-01 2014-11-21 Univ Nat Cheng Kung 含有乾粉狀試劑的血液凝固測試用生醫晶片
CN102645543A (zh) * 2011-02-21 2012-08-22 复旦大学 基于微流控芯片快速检测分析阿米巴抗体的方法及其应用
CN102759621B (zh) * 2011-04-26 2016-02-24 复旦大学 基于微流控芯片的高通量快速检测疟疾血清的方法
CN103897985B (zh) * 2012-12-25 2016-08-10 中国科学院青岛生物能源与过程研究所 活体单细胞分选电子控制系统
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Publication number Priority date Publication date Assignee Title
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CN107525765B (zh) * 2016-06-15 2021-09-07 优志旺电机株式会社 微流路芯片及检体浓度测定装置

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EP1725330A2 (de) 2006-11-29
CN100509165C (zh) 2009-07-08
CA2559913C (en) 2010-05-25
DE502004006225D1 (de) 2008-03-27
WO2005089944A3 (de) 2005-12-08
US7718127B2 (en) 2010-05-18
TW200531919A (en) 2005-10-01
DE102004013161B4 (de) 2008-04-10
TWI295273B (en) 2008-04-01
KR20070012799A (ko) 2007-01-29
JP2007529720A (ja) 2007-10-25
US20080025888A1 (en) 2008-01-31
ATE385852T1 (de) 2008-03-15
DK1725330T3 (da) 2008-06-16
DE102004013161A1 (de) 2005-10-13
EP1725330B1 (de) 2008-02-13
ES2303118T3 (es) 2008-08-01
CA2559913A1 (en) 2005-09-29

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