CN116324367A - 微颗粒捕获装置 - Google Patents
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Abstract
本发明以提供不进行电、特殊操作而仅使含微颗粒液体在流路中流动就能够捕获单个颗粒的微颗粒捕获装置为课题。利用一种微颗粒捕获装置来解决,该微颗粒捕获装置使含微颗粒液体通过来捕获微颗粒,其中,片材构成为具有平面部以及凸部,从入口进入了的含微颗粒液体在片材的平面部的表面上且凸部和与其相邻的另一凸部之间通过,并从出口排出,凸部构成为在平面部上设为层状,各层包含多个凸部,使通过了入口侧的层的含微颗粒液体通过与该入口侧的层相邻的出口侧的层,在各层中形成有捕获部和旁通部,在特定的层中的旁通部的出口侧,作为与其相邻的另一层的一部分而配置有捕获部。
Description
技术领域
本发明涉及一种微颗粒捕获装置。
背景技术
当前,作为调查生物体细胞性质的方法使用整体(bulk)分析。整体分析是指采集/破坏细胞群来分析基因、蛋白质的方法。另一方面,由于该方法包含采集到的全部的细胞的信息,因此作为非目标的细胞的信息也会反映在数据中。另外,近年来,也已知即使是同种的细胞各自的基因表达也会不同,期望确立单细胞水平的分析方法。为了实现这一点,需要单细胞水平的细胞捕获。
作为实现单细胞捕获的方法,有使用介电电泳法并在阱内捕获细胞的方法(参照专利文献1、非专利文献1)、直接操作/捕获细胞的方法等(参照非专利文献2)。
现有技术文献
专利文献
专利文献1:日本特开2012-34641号公报
非专利文献
非专利文献1:森本笃史,et al.《来自转移性乳癌患者的血中循环癌细胞的检测与单细胞基因分析》,TOSOH Research&Technology Review Vol.59(2015)
非专利文献2:斋藤真人,et al.《单细胞分离分析装置的开发》,生物体医工学51(3):211-216,2013
发明内容
发明要解决的技术问题
但是,这些方法对装置需要特殊的结构,且需要熟练的操作技术,进一步难以根据细胞的种类进行筛选。
除了上述这样的调查生物体细胞性质的方法之外,为了分析PM10、PM2.5这样的微颗粒物质、微塑料的颗粒,寻求单一地分离微颗粒的技术。
本发明以解决上述那样的课题为目的。即,本发明的目的在于提供不进行电、特殊操作而仅使含微颗粒液体在流路中流动就能够捕获单个颗粒的微颗粒捕获装置。
用于解决技术问题的方案
本发明为以下的(1)~(2)。
(1)一种微颗粒捕获装置,包括使含微颗粒液体通过并捕获所述含微颗粒液体所包含的微颗粒的片材,其中,
所述片材构成为,具有平面部以及设置于该平面部之上的多个凸部,从入口进入了的所述含微颗粒液体在所述片材的所述平面部的表面上且所述凸部和与其相邻的另一所述凸部之间通过,并从出口排出,
所述凸部构成为,在所述平面部上设置为层状,各层包含多个所述凸部,使通过了入口侧的层的所述含微颗粒液体通过与该入口侧的层相邻的出口侧的层,
在各层中形成有:所述凸部和与该凸部相邻的所述凸部之间的宽度设定为比作为捕获对象的所述微颗粒的直径小的捕获部;所述凸部和与该凸部相邻的所述凸部之间的宽度设定为比所述微颗粒的直径大的旁通部,
在特定的层中的旁通部的出口侧,作为与该特定的层相邻的另一层的一部分配置有捕获部。
(2)根据上述(1)所述的微颗粒捕获装置,其中,从与所述片材的主表面垂直的方向观察的情况下,所述凸部为矩形或大致矩形。
发明效果
根据本发明,能够提供一种在不进行电、特殊操作而仅使含微颗粒液体在流路中流动就能够捕获单个微粒的微颗粒捕获装置。
附图说明
图1是优选的方式的本发明的微颗粒捕获装置中的片材表面的概略图。
图2是图1中的B-B线剖视图。
图3是图1中的部分A的放大图。
图4是在实施例中使用的片材的表面的放大照片。
图5是用实体显微镜观察示出在实施例中捕获到微颗粒的状态而得到的片材的放大照片。
具体实施方式
本发明的微颗粒捕获装置是包括使含微颗粒液体通过并捕获上述含微颗粒液体所包含的微颗粒的片材的微颗粒捕获装置,其中,上述片材构成为,具有平面部以及设置于该平面部之上的多个凸部,从入口进入了的上述含微颗粒液体在上述片材的上述平面部的表面上且在上述凸部和与其相邻的另一上述凸部之间通过,并从出口排出,上述凸部在上述平面部上设为层状,各层包含多个上述凸部,上述凸部构成为使通过了入口侧的层的上述含微颗粒液体通过与该入口侧的层相邻的出口侧的层,在各层中形成有:上述凸部和与其相邻的上述凸部之间的宽度设定为比作为捕获对象的上述微颗粒的直径小的捕获部;上述凸部和与其相邻的上述凸部之间的宽度设定为比上述微颗粒的直径大的旁通部,在特定的层中的旁通部的出口侧,作为与该特定的层相邻的另一层的一部分而配置有捕获部。
关于本发明的微颗粒捕获装置,使用图1~3来说明。
图1是示出本发明的微颗粒捕获装置1中的片材10的主表面的概略图,图2是图1中的B-B线剖视图,图3是图1的部分A的放大图。
图1所例示的本发明的微颗粒装置1包括:片材10;用于向片材10供给含微颗粒液体的入口3;和排出通过了片材10的含微颗粒液体的出口5。本发明的微颗粒捕获装置的结构不限定于图1所例示的结构,例如图1所示的本发明的微颗粒捕获装置1的整体也可以被箱体覆盖。
如图1、图2所示,本发明的微颗粒捕获装置1中的片材10包含平面部12和设置于其上的多个凸部14。
如图2所示,凸部14的高度(h)优选为5~50μm,更优选为8~20μm。
在这样的本发明的微颗粒捕获装置1中,通过泵、静水压力、电渗流等,从入口3进入了的含微颗粒液体朝向出口5流动,但是在该过程中,该含微颗粒液体在片材10的平面部12的表面上且在凸部14和与其相邻的另一凸部14之间流动,从而微颗粒被夹在特定的凸部14间而被捕获。
此处含微颗粒液体只要是包含微颗粒的液体就没有特别限定。作为含微颗粒液体,例如可以举出人的血液、血液分散于缓冲液的混合液。另外,可以是分散有几μm~几百μm左右的微颗粒的液体,具体而言,可以举出分散有PM10、PM2.5这样的微颗粒物质的分散液、分散有平均粒径为几μm~几百μm左右的微塑料颗粒的分散液。
另外,如图1所示,凸部14在平面部12上以层状设置。
在图1中,将最靠近入口的层作为第一层,将与第一层相邻的出口侧(下游侧)的层作为第二层。另外,将某层作为第P层,将与第P层相邻的出口侧(下游侧)的层作为第P+1层,将进一步相邻的出口侧(下游侧)的层作为第P+2层。
另外,各层包含多个凸部14。在图1中示出各层包含7个凸部14的例子,但是各层所包含的凸部14的个数并无特别限定。进一步,层数也无特别限定。
从入口3进入了本发明的微颗粒捕获装置1的含微颗粒液体在平面部12的表面上流动,首先通过第一层中的凸部14间的流路,接下来通过第二层中的凸部14间的流路。之后同样地构成为通过第P层中的凸部14间的流路,接下来通过第P+1层中的凸部14间的流路。
片材的大小、材质并无特别限定。例如可以由硅橡胶、丙烯酸树脂、聚碳酸酯、环状烯烃聚合物、环状烯烃共聚物、聚苯乙烯、聚乙烯、聚对苯二甲酸乙二醇酯等树脂形成,优选为树脂贴附于玻璃等基板的形态。
图3是本发明的微颗粒捕获装置的情况下的图1的部分A的放大图。
如图3所示,在本发明的微颗粒捕获装置的各层中形成有:凸部14和与其相邻的凸部14之间的宽度(流路的宽度)L1设定为比作为捕获对象的微颗粒的直径小的捕获部21;凸部14和与其相邻的凸部14之间的宽度(流路的宽度)宽度L2设定为比作为捕获对象的微颗粒的直径大的旁通部23。
需要说明的是,第P层与第P+1层的宽度L3优选为7.5~30μm,更优选为8~15μm。
此处,宽度L3是指第P层与第P+1层的最短距离。
在图3的例中,在第P层、第P+1层、第P+2层的各层中,在多个凸部14之间作为流路交替地形成有捕获部21与旁通部23。但是,在本发明的微颗粒捕获装置中,形成于各层的捕获部与旁通部也可以不如图3那样交替地形成。例如也可以是在层内连续地存在多个捕获部。
进一步,在特定的层中的旁通部23的出口侧,作为与其相邻的另一层的一部分而配置有捕获部21。即,在图3的例子中,在第P层中的旁通部23的出口侧(下游侧)配置有第P+1层中的捕获部21。
如图3中例示的那样,优选在相对于层方向的垂直方向上,第P层中的旁通部23与第P+1层中的捕获部21并列配置。更具体而言,在引出相对于层方向的垂直方向的直线时,优选以该直线通过第P层中的旁通部23和第P+1层中的捕获部21(即,该直线不与凸部14相接)的方式来配置第P层中的旁通部23与第P+1层中的捕获部21。
在图3所示的例子中,原则上,从入口侧(上游侧)流过来并而到达第P层的含微颗粒液体所包含的微颗粒无法通过捕获部21,因此微颗粒的至少一部分被捕获部21捕获。当微颗粒被捕获时该捕获部21闭塞。另一方面,被捕获到的微颗粒以外的成分(包含粒径更小的微颗粒)通过第P层的捕获部21而到达第P+1层。另外,到达了第P层的含微颗粒液体所包含的全部成分能够通过旁通部23。由此,没有被第P层的捕获部21捕获到的微颗粒通过第P层的旁通部23而到达第P+1层,且上述微颗粒的至少一部分被第P+1层中的捕获部21捕获。此处,在第P层中的旁通部23的出口侧(下游侧)配置有第P+1层中的捕获部21,因此通过了第P层的旁通部23的微颗粒容易被第P+1层的捕获部21捕获。
此处,能够逐层变更捕获部的宽度。
例如,含微颗粒液体包含相对而言大粒径的微颗粒与小粒径的微颗粒,在想要分别捕获并分离的情况下,使片材上的捕获部的宽度在入口侧(上游侧)的层大且在出口侧(下游侧)的层小。在该情况下,只要使入口侧的层中的捕获部的宽度比捕获对象的大粒径的颗粒的直径小,并且比捕获对象外的小粒径的颗粒的直径大,就能够在入口侧的层中的捕获部处逐颗粒地捕获大粒径的微颗粒。虽然小粒径的颗粒会通过入口侧的层中的捕获部,但是只要使出口侧的层中的捕获部的宽度比捕获对象的小粒径的颗粒的直径小,小粒径的颗粒就会被出口侧的捕获部捕获。
在如图1、图3所示的俯视图中(即,在从与片材10的主表面垂直的方向观察本发明的微颗粒捕获装置1的情况下),优选凸部14为图1所示的矩形。另外,优选凸部14为图3所示的大致矩形(将矩形作为基体,其四个角的一部分被直线切掉而被倒角的形状、矩形的四角的至少一部分角被切削而带有圆角的形状)。此处,被直线切掉的倒角部分和以带有圆角的方式切削的倒角部分的面积优选为所捕获的微颗粒的面积(投影面积)的一半以下。
在凸部14为矩形或大致矩形的情况下,到达了已经捕获有微颗粒的捕获部21的其他微颗粒沿着凸部14的表面向层方向移动,从旁通部23向下游侧的相邻的层移动,容易被下游侧的层中的捕获部21捕获。其结果,本发明的发明者发现微颗粒的捕获效率提高。在凸部14不是矩形的情况(例如圆形、椭圆形等情况)下,因为其外形包含R,所以微颗粒会沿着R移动,可能不会向下游侧的相邻的层中的捕获部21移动。
[实施例]
<微颗粒捕获装置的制造>
按照以下所示的顺序制作了微颗粒捕获装置。需要说明的是,片材中的捕获部的宽度在入口侧(上游侧)的层中为15μm,在出口侧(下游侧)的层中为5μm。另外,片材中的旁通部的宽度在上游侧的层中为30μm,在出口侧(下游侧)的层中为10μm,特定的层和与其相邻的另一层的宽度全部为50μm。
首先,使用旋转器在板状的硅晶片的表面均匀涂敷感光性树脂(SU-83050、日本化药公司制)。
接下来,通过掩膜对感光性树脂照射紫外线。
接下来,在95℃下烘烤照到了紫外线的硅晶片上的感光性树脂。
接下来,使用developer(SU-8Developer、日本化药公司制),去除紫外线未照射部,制作模具。
接下来,将硅橡胶(SILPOT184、道康宁公司制)注入模具。
接下来,在100℃且0.5小时的条件下硫化硅橡胶。
接下来,从硅晶片上剥离硅橡胶从而形成流路形成片材。
接下来,在成为入口和出口的部位开冲孔,制作流体导入部,从而制作微颗粒捕获装置。
<接合>
使用光源(L 12530-01、滨松光子学有限公司制),对形成有流路形成片材的玻璃基板两者照射15秒真空紫外光。进一步,通过将双方的照射面贴合从而制作片材。
将用实体显微镜观察制作出的片材而得到的放大照片示出在图4中。
<实验>
将直径为25μm、6μm或1μm的3种聚苯乙烯微球分散在磷酸缓冲液(PBS(-),和光纯药工业公司制)中从而制备试剂。
接下来,使用移液管使试剂流入微颗粒捕获装置。
进一步,用实体显微镜观察微颗粒捕获装置的片材。将用实体显微镜观察而得到的放大照片示出在图5中。需要说明的是,图5的放大倍率与图4的情况相同。
从扩大照片可以确认,在上游侧的层的捕获部处能够单一地捕获直径为25μm的聚苯乙烯微球,在下游侧的层的捕获部处能够单一地捕获直径为6μm的聚苯乙烯微球。
本申请主张基于2020年9月29日申请的日本专利申请特愿2020-163376的优先权,并将其公开的全部纳入于此。
附图标记说明
1本发明的微颗粒捕获装置
3入口
5出口
10 片材
12 平面部
14 凸部
21 捕获部
23 旁通部
Claims (2)
1.一种微颗粒捕获装置,包括使含微颗粒液体通过并捕获所述含微颗粒液体所包含的微颗粒的片材,其中,
所述片材构成为,具有平面部以及设置于所述平面部之上的多个凸部,从入口进入了的所述含微颗粒液体在所述片材的所述平面部的表面上且所述凸部和与该凸部相邻的另一所述凸部之间通过,并从出口排出,
所述凸部构成为,在所述平面部上设为层状,各层包含多个所述凸部,使通过了入口侧的层的所述含微颗粒液体通过与所述入口侧的层相邻的出口侧的层,
在各层中形成有:所述凸部和与该凸部相邻的所述凸部之间的宽度设定为比作为捕获对象的所述微颗粒的直径小的捕获部;所述凸部和与该凸部相邻的所述凸部之间的宽度设定为比所述微颗粒的直径大的旁通部,
在特定的层中的旁通部的出口侧,作为与该特定的层相邻的另一层的一部分而配置有捕获部。
2.根据权利要求1所述的微颗粒捕获装置,其中,
从与所述片材的主表面垂直的方向观察的情况下,所述凸部为矩形或大致矩形。
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