CN107003329A - 微细送液结构体、以及分析装置 - Google Patents
微细送液结构体、以及分析装置 Download PDFInfo
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Abstract
本发明提供一种微细送液结构体,多个微细突起(60)排成一列,并且周期性地设置以相邻的微细突起(60)的间隙作为送液路(61)的单元列,以使各个微细突起(60)的间隔为引起毛细管现象的间隔的方式排列,对每个单元列,将送液路(61)中的至少一条设为与其他送液路(61b)相比使流动阻力相对地降低了的低流动阻力送液路(61a),并且以将低流动阻力送液路(61a)沿着给定的送液方向配置的方式,排列微细突起(60)。由此,可以不在送液方向上产生偏向地再现性良好地任意控制送液方向。
Description
技术领域
本发明涉及作为移送液体的推进力利用了毛细管现象的微细送液结构体,特别涉及可以任意控制液体的移送方向的微细送液结构体、以及具备此种微细送液结构体的分析装置。
背景技术
例如,专利文献1中,提出过如下的微细结构,即,以引起毛细管现象的间隔配置多个微细突起,构成将毛细管现象作为用于液体的移送的推进力来利用的液体的流动系统。
另外,非专利文献1中,研究过在此种利用了毛细管现象的流动系统(毛细管泵)中控制液体的流动性。
现有技术文献
专利文献
专利文献1:日本特表2005-532151号公报
非专利文献
专利文献2:Capillary pumps for autonomous capillary systems;Lab on aChip,2007,7,119-125
发明内容
发明所要解决的问题
然而,本发明人等进行验证的结果是,即使是非专利文献1的流动系统,也不足以再现性良好地控制液体的流动性。例如,将非专利文献1中所例示的液体流经毛细管泵的内部的样子的一例表示于图10中,在非专利文献1的流动系统的情况下,如图10所示,会在送液方向上产生偏向(偏り),在非专利文献1的Fig.4(a)中也表示有同样的图。
本发明人等反复进行了深入研究,结果得到如下的看法,即,产生此种送液方向的偏向可能是起因于,在液体流经相邻的各个微细突起之间时,在其流动阻力方面没有差别,送液方向不确定。
本发明是鉴于上述的事情而完成的,其目的在于,提供一种微细送液结构体,是以引起毛细管现象的间隔排列多个微细突起而成的微细送液结构体,通过对形成于微细突起之间的送液路的流动阻力赋予差别,而可以任意控制送液方向,此外还提供具备此种微细送液结构体的分析器件。
用于解决问题的方法
本发明的微细送液结构体是以引起毛细管现象的间隔排列多个微细突起而成的微细送液结构体,采用了如下的构成,即,所述微细突起排成一列,并且周期性地设置以相邻的所述微细突起的间隙作为送液路的单元列,对每个所述单元列,将所述送液路中的至少一条设为与其他送液路相比相对地降低了流动阻力的低流动阻力送液路,并且将所述低流动阻力送液路沿着给定的送液方向配置。
本发明的分析装置具备如上所述的微细送液结构体,形成利用所述微细送液结构体获得推进力而输送包含分析对象的调配液的构成。
发明效果
根据本发明,在利用以引起毛细管现象的间隔排列多个微细突起而成的微细送液结构体获得送液的推进力时,可以不在其送液方向上产生偏向地再现性良好地任意控制送液方向。
附图说明
图1是表示本发明的实施方式的分析装置的一例的立体图。
图2是表示本发明的实施方式的分析装置的一例的分解立体图。
图3是本发明的实施方式的分析装置的一例的检测部的说明图。
图4是本发明的实施方式的分析装置的一例的基板的示意俯视图。
图5是对本发明的实施方式的微细送液结构体的一例将其要部放大表示的示意俯视图。
图6是对钉扎效果(ピン止め)进行说明的说明图。
图7是表示在本发明的实施方式的微细送液结构体的一例中液体流动的样子的说明图。
图8是表示在本发明的实施方式的微细送液结构体的一例中任意地引导送液方向的例子的说明图。
图9是针对本发明的实施方式的分析装置的一例的检测部的其他例子的说明图。
图10是表示在现有的微细送液结构体的一例中液体流动的样子的说明图。
具体实施方式
以下,在参照附图的同时,对本发明的优选的实施方式进行说明。
[分析装置]
图1是表示本实施方式的分析装置的一例的立体图,图2是其分解立体图。
这些图所示的例子中,分析装置1被作为基于免疫层析法的流感诊断试剂盒构成,具备:基板2、覆盖基板2的表面的覆盖体3、浸渗有与流感抗原结合的胶体金标记抗体的结合垫4、和吸收分析后的残液的吸收垫5。
在基板2的表面,形成有结合垫抵接部4a、第一毛细管泵部6a、送液流路部7、检测部8、第二毛细管泵部6b、以及吸收垫抵接部5a。
在检测部8中,设有涂布有捕捉与胶体金标记抗体结合了的流感抗原的捕捉抗体的测试流路8a、和涂布有捕捉没有结合流感抗原的胶体金标记抗体的捕捉抗体的对照流路8b。测试流路8a例如如图3所示,以宽幅浅底形成,在其底面涂布捕捉抗体CA,由此可以容易地捕捉与胶体金标记抗体结合了的流感抗原LA。虽然没有特别地图示,然而可以将对照流路8b也设为相同。
而且,图3(b)是图3(a)的A-A剖视图。
另外,第一毛细管泵部6a和第二毛细管泵部6b由作为输送包含分析对象的调配液的推进力利用毛细管现象的微细送液结构体构成,对于该微细送液结构体将在后面叙述。
而且,图4是基板2的示意俯视图,图中在以网点表示的部位形成微细送液结构体。基板2只要是可以良好地转印形成微细形状,则可以使用聚二甲基硅氧烷等紫外线固化性、热固性或双组份固化性树脂利用流延成形来成形,也可以使用聚甲基丙烯酸甲酯、聚苯乙烯、聚碳酸酯、环烯烃共聚物、环烯烃聚合物等热塑性树脂利用注射成形、纳米压印等来成形。另外,也可以使用玻璃或硅利用蚀刻、超精密机械加工等来成形。
覆盖体3可以设为树脂制或玻璃制,优选为透明到可以透视形成于基板2的表面的检测部8的程度。该覆盖体3在形成于一端侧的缺口部4b、5b中分别保持结合垫4和吸收垫5的同时,将第一毛细管泵部6a、送液流路部7、检测部8(测试流路8a及对照流路8b)、第二毛细管泵部6b密封地与基板2接合。
此时,以使由覆盖体3密封了的第一毛细管泵部6a在结合垫抵接部4a侧开口的方式,将结合垫抵接部4a制成与第一毛细管泵部6a的底面相同的深度,或比该底面略深。由此,借助该开口,将结合垫4与第一毛细管泵部6a连接。
同样,以使由覆盖体3密封了的第二毛细管泵部6b在吸收垫抵接部5a侧开口的方式,将吸收垫抵接部5a制成与第二毛细管泵部6b的底面相同的深度,或比该底面略深。由此,借助该开口,将吸收垫5与第二毛细管泵部6b连接。
在使用此种分析装置1诊断被测者是否感染了流感时,首先,将包含从被测者采集的鼻涕等样品(分析对象)的样品调配液向结合垫4滴下。
滴加到结合垫4的样品调配液从结合垫4渗出后渗入第一毛细管泵部6a。此后,样品调配液以毛细管现象作为推进力在第一毛细管泵部6a内行进而被送向送液流路部7。送到送液流路部7的样品调配液利用毛细管现象流过送液流路部7内,被送向形成于该流路上的检测部8。
当通过了检测部8的样品调配液的残液到达第二毛细管泵部6b时,就会以其毛细管现象作为推进力在第二毛细管泵部6b内行进。
此时,如果样品调配液的流动长度增加,则流动阻力也会随之累积地增加而使样品调配液的送液速度降低,以如图所示的底部展开状(末広がり)形成第二毛细管泵部6b,在后述的微细送液结构体中形成于微细突起60间的送液路61的数目沿着流动方向增加,由此可以抑制由流动阻力造成的送液速度的降低。通过如此设置,就可以不使用外部泵地以一定的流量输送样品调配液,从而能够实现再现性高的分析(诊断)。
样品调配液的残液在第二毛细管泵部6b内行进后由吸收垫5吸收。
当将样品调配液向结合垫4滴下时,浸渗于结合垫4中的胶体金标记抗体就会向样品调配液中溶出。此后,如果患者感染了流感,则会在样品调配液中含有流感抗原,溶出到样品调配液中的胶体金标记抗体的一部分与流感抗原结合,与没有结合流感抗原的剩下的胶体金标记抗体一起,被送向形成于送液流路部7的流路上的检测部8。
如前所述,在检测部8中,设有涂布有捕捉与胶体金标记抗体结合了的流感抗原的捕捉抗体的测试流路8a、和涂布有捕捉没有结合流感抗原的胶体金标记抗体的捕捉抗体的对照流路8b。因此,在样品调配液通过检测部8后,如果仅在对照流路8b中可以看见由胶体金粒子造成的发色,则可以诊断为被测者没有感染流感,如果在测试流路8a中也可以看到由胶体金粒子造成的发色,则可以诊断为被测者感染了流感。
[微细送液结构体]
然后,在前述的分析装置1中,对作为送液的推进力利用毛细管现象输送包含分析对象的调配液的微细送液结构体进行说明。
图5是对本实施方式的微细送液结构体的一例将其要部放大表示的示意俯视图。在该微细送液结构体中,多个微细突起60排成一列,并且周期性地设置以相邻的微细突起60的间隙作为送液路61的单元列,以使各个微细突起60的间隔为引起毛细管现象的间隔(例如,在一个单元列中相邻的微细突起60之间的间隔为1~1000μm,相邻的单元列间的间隔为1~1000μm)的方式排列。
而且,图5所示的例子中,微细突起60设为纵120μm、横30μm、高30μm,将一个单元列中相邻的微细突起60之间的间隔设为30μm,将相邻的单元列间的间隔设为60μm。在前述的分析装置1中,微细突起60的高度相当于包含本实施方式的微细送液结构体的第一毛细管泵部6a、第二毛细管泵部6b的底面的深度,微细突起60的头端与覆盖体3密接。由此,微细突起60的周围的空间就由覆盖体3密封。
另外,本实施方式中,以使形成于一个单元列中的送液路61与形成于与之相邻的单元列中的送液路61如图所示地位于交错的位置的方式均等地排列微细突起60。通过如此设置,当液体利用毛细管现象通过形成于一个单元列中的送液路61、其液面与相邻的单元列的微细突起60接触时,就会反复发生液体利用毛细管现象在这些单元列之间扩散的现象。此外,通过设为上述排列,借助毛细管现象的液体的送液路就被以并联回路状形成,与以串联回路状形成送液路的情况相比,可以降低流动阻力,因此可以高效地获得利用了毛细管现象的送液的推进力。
另外,图5所示的例子中,在形成送液路61而相邻的微细突起60中,在各条送液路61的出口侧,形成体现出钉扎效果的边缘部62。
此处,所谓钉扎效果,如图6所示,是指如下的现象,即,当以接触角θ在平面中行进的液面到达边缘部时(参照图6(a)),在将平面与边缘部的外侧的面的夹角设为α时,直到接触角变为θ+(π-α)(参照图6(b))后,该液面才会越过边缘部,本实施方式中,将此时的平面与边缘部的外侧的面的夹角α定义为钉扎角。
图5所示的例子中,通过恰当地设定形成于送液路61的出口侧的边缘部62的钉扎角,而在一个单元列中,将形成于各个微细突起60之间的送液路61中的至少一条设为与其他送液路61b相比相对地降低了流动阻力的低流动阻力送液路61a。
即,对于形成除去低流动阻力送液路61a以外的其他送液路61b而相邻的微细突起60b、60c,通过使其在该送液路61b的出口侧形成的边缘部62b的钉扎角小于形成低流动阻力送液路61a而相邻的微细突起60a、60b的在该低流动阻力送液路61a的出口侧形成的边缘部62a的钉扎角,而使低流动阻力送液路61a的流动阻力与其他送液路61a的流动阻力相比相对地降低。
而且,图5所示的例子中,将微细突起60a设为矩形,在两端形成钉扎角90°的边缘部62a。另外,微细突起60b在一端形成钉扎角90°的边缘部62a,在另一端形成钉扎角45°的边缘部62b,微细突起60c在两端形成钉扎角45°的边缘部62b。对于边缘部62a、62b的头端,也可以以不妨碍钉扎效果的体现的程度形成R形状。
另外,图5所示的例子中,对每个单元列,将送液路61中的至少一条设为与其他送液路61b相比相对地降低了流动阻力的低流动阻力送液路61a,并且以沿着给定的送液方向配置低流动阻力送液路61a的方式,排列微细突起60a、60b、60c。与此同时,恰当地调整相邻的单元列间的间隔(例如,考虑到形成低流动阻力送液路61a而相邻的微细突起60a、60b间的间隔地拓宽)等,使形成于单元列间的列间送液路61c的流动阻力与低流动阻力送液路61a的流动阻力相比相对地降低。
通过如此设置,就会如图7所示,液体优先地通过形成于一个单元列中的送液路61当中的流动阻力低的低流动阻力送液路61a(参照图7(a)~(c)),以此为开端,液体利用毛细管现象向形成于该单元列与下一个单元列之间的列间送液路61c展开(参照图7(c)~(e)),由于列间送液路61c的流动阻力最低,因此在列间送液路61c被液体充满之前,液体的前端不会向形成于下一个单元列与再下一个单元列之间的列间送液路61c行进(参照图7(e))。此后,当列间送液路61c被液体充满时,液体就会优先通过下一个单元列的低流动阻力送液路61a(参照图7(f)),利用该现象的反复进行,液体流动下去(参照图7(f)~(h))。
由此,根据本实施方式,就可以不在送液方向上产生偏向地再现性良好地控制利用毛细管现象送液时的流动性。
另外,前述的分析装置1中,将第一毛细管泵部6a和第二毛细管泵部6b分别制成等腰三角形,沿着从其顶点向底边做出的垂线配置低流动阻力送液部61a,由此可以高效地获得利用了由微细送液结构体造成的毛细管现象的送液的推进力,低流动阻力送液部61a的配置可以根据所期望的送液方向恰当地设定。
例如,在如图8(a)所示欲使送液方向弯曲的情况下,或如图8(b)所示欲使送液方向分支为两个以上的方向的情况下,通过沿着图中以虚线表示的方向配置低流动阻力送液部61a,就可以将送液方向向任意的方向引导。
如此所述,根据本实施方式,在利用以引起毛细管现象的间隔排列多个微细突起而成的微细送液结构体获得送液的推进力时,可以不在其送液方向上产生偏向地再现性良好地任意控制送液方向。
以上,对于本发明,通过给出优选的实施方式而进行了说明,然而本发明当然并不限定于前述的实施方式,可以在本发明的范围中实施各种变更。
例如,在前述的微细送液结构体的实施方式中,为了使低流动阻力送液路61a的流动阻力与其他送液路61b的流动阻力相比相对地降低,在形成送液路61而相邻的微细突起60的该送液路61的出口侧,形成体现出钉扎效果的边缘部62,通过恰当地设定边缘部62的钉扎角,而使低流动阻力送液路61a的流动阻力与其他送液路61b的流动阻力相比相对地降低,然而并不限定于此。
为了使低流动阻力送液路61a的流动阻力与其他送液路61b的流动阻力相比相对地降低,例如也可以如下所示地设置。
1)仅在形成其他送液路61b而相邻的微细突起60中,在该送液路61b的出口侧形成体现出钉扎效果的边缘部62,例如,将形成低流动阻力送液路61a而相邻的微细突起的该送液路61a的出口侧的形状制成不体现出钉扎效果的R形状等,而使低流动阻力送液路61a的流动阻力与其他送液路61b的流动阻力相比相对地降低。
2)通过对形成其他送液路61b而相邻的微细突起60的送液路61b侧的部位实施疏水处理来提高流动阻力,而使低流动阻力送液路61a的流动阻力与其他送液路61b的流动阻力相比相对地降低。
3)通过增大低流动阻力送液路61a的截面积,而使低流动阻力送液路61a的流动阻力与其他送液路61b的流动阻力相比相对地降低。
另外,在使形成于单元列间的列间送液路61c的流动阻力与低流动阻力送液路61a的流动阻力相比相对地降低时,在前述的实施方式中,举出恰当地调整相邻的单元列间的间隔的例子,然而并不限定于此。也可以使用上述1)~3)中所示的方法等,使列间送液路61c的流动阻力与低流动阻力送液路61a的流动阻力相比相对地降低。
另外,微细突起60的形状并不限定于前述的实施方式,可以在不妨碍本发明的效果的范围中恰当地设计。
另外,在前述的分析装置的实施方式中,对将设于检测部8的测试流路8a和对照流路8b制成宽幅浅底、并在其底面涂布了捕捉抗体的例子进行了说明,然而并不限定于此。也可以如图9所示,在设于检测部8的测试流路8a和对照流路8b中都形成如前所述的微细送液结构体,控制通过这些流路8a、8b的样品调配液的送液方向。此时,通过在微细突起60上也涂布捕捉抗体CA,例如,在测试流路8a中,就会更容易捕捉与胶体金标记抗体结合了的流感抗原LA,并且由于与胶体金标记抗体结合了的流感抗原LA也被沿着微细突起60的高度方向捕捉,因此更容易看到由胶体金粒子造成的发色。
而且,图9(b)是图9(a)的B-B剖视图。
另外,在前述的分析装置的实施方式中,以流感诊断试剂盒为一例举出而进行了说明,然而并不限定于此。可以应用于作为送液机构不使用外部泵、在输送包含分析对象的调配液时要求将毛细管现象作为推进力利用的各种分析装置中。
[实施例]
下面,举出具体的实施例,对本发明进行更详细的说明。
[实施例]
向利用光刻法实施微细加工而制作的注塑模中,浇注聚二甲基硅氧烷(DowCorning Toray公司制SILPOT184;与固化剂的重量比为10:1),成形出在表面转印形成有与图5所示的例子相同的排列的毛细管泵(微细送液结构体)的基板。在如此得到的基板的表面,利用聚二甲基硅氧烷的自吸附密合作为覆盖体的大型载玻片(松浪硝子工业公司制)而将毛细管泵密封。
[比较例1]
除了将全部的微细突起设为与图5所示的例子中的微细突起60a相同的微细突起而排列,将所得的毛细管泵转印形成于基板表面以外,与实施例1相同。
[比较例2]
除了将全部的微细突起设为与图5所示的例子中的微细突起60c相同的微细突起而排列,将所得的毛细管泵转印形成于基板表面以外,与实施例1相同。
[评价]
作为调配液使用3%TRITON-X100(Dow Chemical公司制),从设于覆盖体中的投入口以5μL的滴加量滴加。利用数码显微镜(Keyence公司制VHK-1000)拍摄借助毛细管力流经毛细管泵内的调配液,测定调配液通过毛细管泵的时间,算出流量的偏差(CV)。进行5次测定,将其平均值表示于表1中。在上述CV为5%以下的情况下,作为可以实现稳定的送液的良好的微细送液结构体将评价设为“○”,将上述CV大于5%的样品的评价设为“×”,一并表示于表1中。
[表1]
产业上的可利用性
本发明并不限定于流感诊断试剂盒等医疗领域中的分析装置,可以适用于各种领域中的分析装置。
对于该说明书中记载的文献及成为本申请的巴黎优先权的基础的日本申请说明书的内容全都引用到本说明书中。
符号的说明
1分析装置,
60(60a、60b、60c)微细突起,
61送液路,
61a低流动阻力送液路,
61b其他送液路,
61c列间送液路,
62(62a、62b)边缘部
Claims (7)
1.一种微细送液结构体,其特征在于,
是以引起毛细管现象的间隔排列多个微细突起而成的微细送液结构体,
所述微细突起排成一列,并且周期性地设置以相邻的所述微细突起的间隙作为送液路的单元列,
对每个所述单元列,将所述送液路中的至少一条设为与其他送液路相比相对地降低了流动阻力的低流动阻力送液路,并且
沿着给定的送液方向配置所述低流动阻力送液路。
2.根据权利要求1所述的微细送液结构体,其特征在于,
使形成于所述单元列间的列间送液路的流动阻力与所述低流动阻力送液路的流动阻力相比相对地降低。
3.根据权利要求1或2所述的微细送液结构体,其特征在于,
在形成除去所述低流动阻力送液路以外的其他送液路而相邻的所述微细突起的该送液路的出口侧,形成体现出钉扎效果的边缘部,
由此使所述低流动阻力送液路的流动阻力与其他送液路的流动阻力相比相对地降低。
4.根据权利要求1或2所述的微细送液结构体,其特征在于,
在形成所述送液路而相邻的所述微细突起的所述送液路的出口侧,形成体现出钉扎效果的边缘部,
使形成除去所述低流动阻力送液路以外的其他送液路而相邻的所述微细突起中形成的所述边缘部的钉扎角小于形成所述低流动阻力送液路而相邻的所述微细突起中形成的所述边缘部的钉扎角,
由此使所述低流动阻力送液路的流动阻力与其他送液路的流动阻力相比相对地降低。
5.根据权利要求1或2所述的微细送液结构体,其特征在于,
对形成除去所述低流动阻力送液路以外的其他送液路而相邻的所述微细突起的该送液路侧的部位实施疏水处理,
由此使所述低流动阻力送液路的流动阻力与其他送液路的流动阻力相比相对地降低。
6.根据权利要求1或2所述的微细送液结构体,其特征在于,
使所述低流动阻力送液路的截面积大于除去所述低流动阻力送液路以外的其他送液路的截面积,
由此使所述低流动阻力送液路的流动阻力与其他送液路的流动阻力相比相对地降低。
7.一种分析装置,其特征在于,
具备权利要求1~5中任一项所述的微细送液结构体,利用所述微细送液结构体获得推进力来输送包含分析对象的调配液。
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TW201632258A (zh) | 2016-09-16 |
JPWO2016084381A1 (ja) | 2017-09-07 |
WO2016084381A1 (ja) | 2016-06-02 |
TWI670114B (zh) | 2019-09-01 |
JP6601416B2 (ja) | 2019-11-06 |
EP3226003A4 (en) | 2018-06-20 |
CN107003329B (zh) | 2019-05-31 |
KR101996078B1 (ko) | 2019-07-03 |
KR20170073695A (ko) | 2017-06-28 |
US20170259259A1 (en) | 2017-09-14 |
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