CN101048338A - 由两块板构成的流体容器 - Google Patents

由两块板构成的流体容器 Download PDF

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CN101048338A
CN101048338A CNA2005800367753A CN200580036775A CN101048338A CN 101048338 A CN101048338 A CN 101048338A CN A2005800367753 A CNA2005800367753 A CN A2005800367753A CN 200580036775 A CN200580036775 A CN 200580036775A CN 101048338 A CN101048338 A CN 101048338A
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plate
ridge
cover plate
fluid container
structured
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CN101048338B (zh
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赖因霍尔德·温贝格尔-弗里德尔
克里斯蒂亚尼·德维茨
E.·A.·W.·扬森
伯纳德斯·雅各布斯·约翰内斯·范耶塞尔
巴尔特·范尼内恩
马里纳斯·伯纳德斯·奥尔德里克因克
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Koninklijke Philips NV
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Abstract

本发明涉及一种微型化流体容器，其具有以脊(13、14)为边界的微通道(11、12)，其中所述脊(13、14)的顶部粘合到盖板(20)。可以通过在微通道(11、12)之间的空腔中分布胶(33)来实现额外的稳定性，所述胶的散布是由毛细管力来驱动的。

Description

由两块板构成的流体容器
技术领域
本发明涉及一种由结构化板(structured plate)和盖板构成的具有微通道的微型化流体容器以及一种用于制造这种容器的方法。
背景技术
在越来越多的任务中用到微型化流体容器，在药物、化学物质或生化样品的分析当中尤其如此。生产这种容器的典型方式为将所需结构例如微通道蚀刻到板中，并将所述结构化板与平坦盖板放置在一起。
例如，在WO 01/54810A1中对这种方法进行了描述，其中盖板涂有热胶(thermoglue)，在将盖板和结构化板放置在一起之后使所述热胶固化。这种方法的两个主要缺点在于，由于部件和胶厚度的偏差，对通道高度的控制不佳；以及内通道表面上的热负载可能会破坏装置工作所需的某些(生物)化学处理。还可能将胶挤入微通道内，或者由于过程控制不良而产生局部的空隙。
发明内容
鉴于这种情况，本发明的目的是提供一种具有微通道的可再现的一定尺度的微型化流体容器和制造其的简单方法。
该目的是通过根据权利要求1所述的微型化流体容器和根据权利要求9所述的方法实现的。在从属权利要求中公开了优选实施例。
根据其第一方面，本发明涉及一种微型化流体容器，其中术语“微型化”是指这样的情况：容器结构(尤其是其微通道)的尺度在1到1000μm的范围内，优选在10到100μm的范围内。或者，可以说将微型化流体容器设计成处理体积通常为100nl到1ml的样品。该流体容器包括以下部件：
a)所谓的“结构化板”，其特征在于从该板的一侧(优选以大约90°的角)突出的至少两个相邻的脊，其中所述脊的顶部处于相同的高度，即，处在与结构化板的主平面平行的同一平面内。此外，所述脊构成流体容器的微通道的两个边界，其中微通道通常为更大的微通道系统和其他空腔的一部分。
应该注意的是，要在局部的基础上来理解“相邻脊”的上述特征，即，所述至少两个脊实际上可以是形成环路的一个长的连续脊的一部分。
b)“盖板”，例如通过粘结将所述盖板附着到所述结构化板，并且该盖板在所述至少两个脊的顶部与它们接触，其中顶部和盖板之间的接触区优选埋入密封材料中。盖板与结构化板接触的一侧尤其可以是平坦的(完全地或者至少在接触区中是平坦的)。此外，盖板可以直接接触所述脊的顶部，任选的密封材料围绕在接触区周围，或者，在盖板和顶部之间可以有(一小段)距离，该距离被任选的密封材料填充。例如，结构化板和/或盖板可以由玻璃、硅或适当的聚合物制成。
在上述流体容器中，微通道是以终止于同一高度的相对较窄的脊为边界。这确保了是在脊的顶部支撑盖板，而不是在距微通道某一距离的或多或少随机分布的点处支撑盖板。此外，脊本身非常适于进行超声波焊接，其中在磨擦点，即结构化板和盖板之间的接触区，振动能被转换为热。在这种情况下，无需加热周围区域脊材料即可局部地熔化，而且不需要胶。如果施加密封材料，将顶部和盖板之间的接触区埋入所述材料中保证了微通道的紧密封闭，所述微通道具有确定的尺度，尤其具有由脊的高度确定的高度。所述板还可以具有集成的有源元件，用于流体的操控和检测。
原则上，脊可以具有任何的形状或截面，例如矩形、梯形、半圆形等。优选地，脊的宽度(或者更一般地，在脊具有宽度不均匀的截面时为平均宽度)与脊的长度(从相关微通道的底部到脊的顶部所测得的长度)之比在0.1∶1到1∶0.1的范围内。换言之，脊的宽度相应地在其高度的0.1和10倍之间，更优选在其高度的0.3和3倍之间。
对于尖的锥形脊而言，顶部相当于线。然而，在优选实施例中，脊的顶部是平坦的，例如具有窄条的形式。所述顶部的宽度(沿着相关微通道相对于脊的延伸横向地测量)通常在脊的平均宽度的大约0.1到1倍的范围内。具有平坦顶部的脊更容易以精确的高度生产且提供更大更好的与盖板的接触区。
任选的密封材料的目的是埋入脊和盖板之间的接触区，从而补偿其中任何的表面不规则并密封连接。为了实现这些目的，密封材料在制造期间优选具有柔软的(例如液体或塑料)稠度(consistency)，从而其可以容易地适应脊和盖板的形状。在优选实施例中，密封材料为胶，其密封连接，并同时在固化时将结构化板固定到盖板。为此目的可以施加多种胶，从PSA(压敏粘合剂)、热塑材料，到交联材料，例如环氧树脂或丙烯酸酯，可以通过照射或加热或在混合时将其固化。可紫外固化的丙烯酸酯的优点在于，可以在任一点及时地启动固化反应，并且以这种方法使胶和组件的施加不受化学反应的影响。
为了提供或改善盖板到结构化板的附着，可以用胶部分地或完全地填充板间的剩余空腔。
根据流体容器的优选实施例，结构化板和/或盖板包括至少一个开口，该开口直接或间接地通到由脊限定的微通道。
本发明还涉及一种制造微型化流体容器，尤其是上述种类的流体容器的方法。该方法包括如下步骤：
a)制备结构化板，所述结构化板具有至少两个相邻的脊，所述脊从该板的一侧突出，其顶部处于同样的高度，且所述脊形成在它们之间的微通道或作为该微通道的边界。
b)提供盖板，其例如可以只是平坦的，或者可以是结构化的。
c)将结构化板和盖板放置在一起，使得脊的顶部接触盖板。在这种状态下，例如通过超声波焊接还可以使两块板永久地彼此相连。
上述方法允许生产上述种类的流体容器。因此参考前面对所述容器进行的说明以获得更多的关于所述方法、其改进和优点的信息。
根据该方法的优选实施例，在步骤c)之前向结构化板的脊的顶部和/或盖板的一侧施加密封材料(例如液体胶)。密封材料优选在施加期间具有柔软的稠度且在步骤c)之后固化。然后密封材料(仅)埋住两块板之间的接触区。
可以通过任何适当的方法实现向脊的顶部施加密封材料。优选地，通过将脊的顶部浸入到液体密封材料层中来使脊的顶部具有密封材料。所述层可以是更深的密封材料池的表面，或者是分布在载体的平坦表面上的相对较薄的液体密封材料层。后一种选择具有以下优点：可以通过载体上的层厚度容易地控制浸入深度，从而防止密封材料过度浸润结构化板。
根据该方法的进一步发展，通过毛细管力利用胶填充在步骤b)中将结构化板和盖板放置在一起之后仍保留在其间的至少一个空腔。所述胶可以提供或者至少加强结构化板和盖板之间所需的连接。由于结构化板中的微通道被脊上的盖板和密封材料紧密地封闭，因此防止多余的胶不利地散布到微通道中。
附图说明
在下文中，借助附图以举例的方式对本发明进行说明，附图中：
图1示出根据本发明的流体容器的制造的第一步骤，即将结构化板浸入胶中；
图2和3示出第二步骤，即组装结构化板和盖板；
图4示出第三步骤，将多余的胶散布在流体容器的空腔中。
具体实施方式
从电子冷却到生物传感器，许多领域都对微流体装置有极大的兴趣。通常，通过在一个基板(例如硅、玻璃或塑料)中形成沟槽并用平坦盖板覆盖该结构化基板来制造所述装置的微通道。对于微小通道而言，具有很高的通道精确度是至关重要的(因为流阻与通道高度的四次方成比例)，通道的精确度不仅由基板的结构化决定，而且还由盖的结合过程决定。
基本上，可以使用多种技术进行结合，或者是直接结合或者是间接结合，直接结合意味着盖和基板直接粘合，在间接结合中使用额外的“胶”层实现结合。直接技术在可能的材料组合上受到限制。为了获得低成本装置，基板通常由塑料制成。
塑料直接结合只能通过热过程实现，其中必须要局部地熔化材料以实现良好的接触和足够的强度。可以通过热表面、辐射、超声波、或激光辐射的吸收来提供用于熔化的能量。仅能利用热塑材料实现熔化，不包括交联材料。局部地熔化微通道的表面破坏了在结合之前进行的任何表面处理。熔化总是伴随有变形，而且由于在所加负载下的蠕变(creep)或从模制中恢复，基板中会存在应力。热结合总是需要压力以确保良好的接触。在实践中，由于结构化基板的高度和平坦度的容差小，很难局部地控制压力，并且局部压力取决于接触面积，而接触面积还取决于通道布局。
间接结合需要结构化基板和盖之间的胶层。胶的厚度增大了通道高度，必须小心地对其进行控制。胶材料与通道内部接触，通过这种方式影响流动行为，并且可以在化学上干扰通道内部的液体。流动行为受到机械和物理表面特性例如粗糙度和浸润行为的影响。这限制了用于关键性应用例如生物传感器盒的可能材料的数量和应用技术。
尽管胶间接结合对于基于聚合物的流体系统而言是最有吸引力的技术，但是需要解决如下问题，一方面是胶渗透到通道中，另一方面是接触表面的不完全浸润(在通道周围产生毛细管)。需要使胶和通道壁的接触面积最小化。这里所公开的方法提供了完美的通道密封，胶在通道内的暴露达到绝对的可控制的最小化。密封质量与通道布局和微流体系统的尺寸无关。在结合期间不需要施加力。由于接触面积小，胶的收缩不会导致组件的翘曲。由于该应用方法自身是稳定的，因此能够实现合理的部件容差。
图1示出根据本发明的微型化流体容器的制造的第一步骤。该图示意性地示出结构化板10的一小部分的侧视截面，该结构化板10例如可以由透明聚合物基板构成。在板10的下侧，通过本领域公知的方式提供所需的结构。从流体容器的功能部件的角度，在截面中示出两个高度不同的微通道11和12。尽管通常将这种微通道蚀刻或机加工成平坦表面，但是微通道11、12至少部分地以从结构化板10的下侧垂直突出的脊13、14为边界。在所示的实例中，脊13、14具有梯形截面，底部宽而顶部窄，其中所有脊的顶部15、16都是平坦的且处于同一高度(即，在一个平面中)。在这里所示的情况下，脊的平均宽度d大致与它们的高度h相同，典型值为d＝h＝70μm。通常，比值d∶h可以在0.1到10的范围内。
例如，可以通过直接对通道板进行微加工，或者通过然后由模制或压纹技术复制的模板来制造脊13、14。用于制造这种模板的优选技术是所谓的LIGA(光刻、微电铸、微成型(Lithographie，Galvanoformung，Abformung))工艺，由如下步骤组成：对基板上的抗蚀剂材料进行光刻结构化，通过电镀在Ni垫片中复制该结构，以及使用该Ni垫片作为模型插入物以对聚合物进行(注入)模制。作为Ni垫片的替代品，还可以使用深蚀刻的硅或玻璃。
图1还示出被液体胶的薄层31覆盖的载体30。如箭头所示，将结构化板10浸入到所述胶层31中以便利用数量受到控制的胶32覆盖脊13、14的顶部15、16(参考图2)。胶的量取决于顶部的宽度、胶的粘度和浸入深度。
如可以从图2和3所看出的那样，然后将结构化板10与平坦盖板20放置在一起，所述盖板20例如可以由与结构化板10相同的材料构成。盖板20可以是非结构化的，或者可以包含与表面对准的结构，以在需要时实现与脊的接触。脊13、14的顶部15、16与盖板20的内表面(直接)接触，根据盖板20的浸润行为分布胶32。在均衡之后，通过照射或热量使胶固化，以在板10、20之间提供牢固的结合。
如果在结构化板10上微通道11、12之间有大的水平距离，则可能会相应地形成板10、20之间的大的未连接区域。为了改善结合，在这种情况下可以在结构化板10上提供额外的脊，其中这些“伪脊”无需作为微通道的边界，只是为了稳定性。
图4示出另一个步骤，可以任选地执行该步骤以改善结构化板10和盖板20之间的结合。在该步骤中，利用胶33填充在所获得的流体容器中不起作用的空闲空间或空腔。可以通过在流体容器的开放边缘处从喷嘴34施加所述胶33而容易地实现其的分布，从该边缘胶33被毛细管力驱动而分散在盖板20和结构化板10之间。适于该目的的胶需要具有低粘度(10-10000mPa)，以实现毛细管流动，并且它们应当在室温下固化，以避免破坏传感器中的生物材料。氰基-丙烯酸酯、丙烯酸酯、环氧树脂和硅树脂是该应用的合适候选者。两块板10、20之间的间隙应当足够小(大约0.015-0.5mm)，以通过毛细管力实现粘合剂流动。
在未连接到流体容器的边缘的空腔中，可以通过盖板20或结构化板10中的孔(未示出)施加胶33。由于脊13、14和盖板20之间的连接被第一胶32紧密地密封，额外的胶33不能进入到微通道11、12中，并且不可能在其中造成不利影响。
上述方法适用于各种材料组合与通道形状，且已经成功地进行过试验测试。在这种试验中，例如，从注射成型的聚烯烃(Zeonex 48 R)结构和传递成型的环氧树脂基板根据所提出的方法制造微流体通道装置。在硅晶片上旋涂厚度为8μm的胶层(具有引发剂Irgacure的丙烯酸酯混合物)。在利用氧等离子体进行处理之后，将Zeonex结构浸入该胶层中，然后将其转移到环氧树脂基板，在该环氧树脂基板处在不用力的情况下施加所述Zeonex结构并通过紫外光照射使胶固化。类似地，从玻璃基板上的模板利用用于粘合的同一树脂通过UV复制获得通道结构。通过同样的方法成功地将这些结构化样品结合到用氨基硅烷(A1120)处理过的玻璃基板。
在本发明的另一实施例中，可以通过旋涂将胶施加在盖板上，此后将具有脊的结构化板施加在静止的液体胶层中。通过这种方式也避免了通道溢出。这种方法对于盖板不含功能元件的应用是有用的，所述功能元件将被胶层破坏。在这种情况下，在封闭该系统之后，例如为了生物学相互作用需要对通道壁进行特殊处理。
上述结合工艺的周期时间短，使其适于产业化。该工艺中的第一步涉及两个部件的拾取、对准和放置，这将耗时约1到5s。在下一步中，例如通过自动分散(dispensing)施加粘合剂，这耗时约0.5到2s。粘合剂将立即开始流动，并将在大约5s之内实现完全填充。氰基丙烯酸酯粘合剂在室温下于数秒内固化而无需任何附加设备。光固化粘合剂也在数秒内固化，但需要光源。
结构化板10和/或盖板20可以包括出现在微通道11、12内部的开口或孔(未示出)，以便为装填或分散提供来自外部的通路。
上述方法实现了流体容器的可靠而坚固的组装而与流体布局无关。它们对于所有微流体应用都很重要，例如就地诊断装置、生物传感器、气体传感器、电子器件和光源的冷却、芯片上试验室、尤其是那些使用塑料通道材料的应用。
最后要指出，在本申请中，术语“包括”并不排除其他元件或步骤，“一个”并不排除多个，并且单个处理器或其他单元可以完成几个装置的功能。本发明体现在每个新颖的特征以及特征的每种组合之中。此外，权利要求书中的附图标记不应被视为是对权利要求的保护范围的限制。

Claims (11)

1、一种微型化流体容器，包括：
a)结构化板(10)，具有至少两个相邻的脊(13、14)，所述脊从该板的一侧突出，其顶部(15、16)处于同一高度(h)，并且所述脊限定其间的微通道(11、12)；
b)盖板(20)，附着到所述结构化板(10)且与所述至少两个脊(13、14)在其顶部(15、16)接触。
2、根据权利要求1所述的流体容器，其特征在于所述盖板(20)和所述顶部(15、16)之间的接触区埋入在密封材料中，优选埋入在胶(32)中。
3、根据权利要求1所述的流体容器，其特征在于所述脊(13、14)的平均宽度(d)为其平均高度(h)的0.1到10倍。
4、根据权利要求1所述的流体容器，其特征在于所述脊(13、14)的所述顶部(15、16)是平坦的。
5、根据权利要求3所述的流体容器，其特征在于所述脊(13、14)的所述顶部(15、16)的宽度大约为所述脊的所述平均宽度的10％到100％。
6、根据权利要求1所述的流体容器，其特征在于所述盖板(20)接触所述结构化板(10)的表面在所述接触区中基本是平坦的。
7、根据权利要求1所述的流体容器，其特征在于所述结构化板(10)和所述盖板(20)之间的至少一个空腔被胶(33)填充。
8、根据权利要求1所述的流体容器，其特征在于所述结构化板(10)和/或所述盖板(20)包括至少一个通到所述微通道(11、12)的开口。
9、一种制造微型化流体容器的方法，包括以下步骤：
a)制备结构化板(10)，所述结构化板具有至少两个相邻的脊(13、14)，所述脊从该板的一侧突出，其顶部(15、16)处于同一高度(h)，并且所述脊限定其间的微通道(11、12)；
b)提供盖板(20)；
c)组装所述结构化板(10)和所述盖板(20)，使得所述脊的所述顶部(15、16)接触所述盖板(20)。
10、根据权利要求9所述的方法，其特征在于将密封材料(32)施加到所述结构化板(10)的所述脊的所述顶部(15、16)和/或所述盖板(20)的一侧，其中将密封材料(32)施加到所述结构化板(10)的所述脊的所述顶部(15、16)是优选通过将其浸入到液体密封材料层(31)中来完成的。
11、根据权利要求9所述的方法，其特征在于通过毛细管力利用胶(33)填充所述结构化板(10)和所述盖板(20)之间的至少一个空腔。
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