CN108772014B - 一种封闭ewod芯片中液滴多维快速混匀方法 - Google Patents
一种封闭ewod芯片中液滴多维快速混匀方法 Download PDFInfo
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Abstract
一种封闭EWOD芯片中液滴多维快速混匀方法,采用液滴多维混匀电极结构,先驱动两种不同的液滴样本分别从左右两个进样电极进入,依次经过过渡电极到达融合电极,合并为一个大液滴;然后在某一方向或者某几个方向上进行液滴的一次分裂,一次分裂结束后,液滴再次回到融合电极合并为一个大液滴;在与一次分裂垂直或者成一定角度的方向上进行二次分裂,分裂完成后,液滴再次在融合电极上合并;重复分裂、融合,直至得到混合均一的溶液;对融合电极下方的出样电极施加高电压,将混匀的液滴移出融合电极;本发明实现封闭的EWOD系统中液滴的多维分裂——融合,提高混匀效率。
Description
技术领域
本发明属于数字微流控技术领域,具体涉及一种封闭EWOD芯片中液滴多维快速混匀方法。
背景技术
介电润湿(electrowetting on dielectric,EWOD)技术是一种数字微流控技术,可在覆有介电层的电极阵列上任意驱动纳升到微升级液滴。其基本原理是:在外加电压的作用下,液滴与电极表面的接触角发生改变,在液滴内产生不对称力,达到驱动液滴的目的。根据系统是否封闭,EWOD芯片可分为开放系统(open system)和封闭系统(confinedsystem)。开放系统中液滴在下极板上驱动,阻力小、驱动速度快,驱动电压小,但是液滴蒸发大,无法实现液滴的发配和分裂;封闭系统中液体在两层平板中驱动,阻力增大,所需驱动电压相应较大,但是可实现液滴的发配、移动、融合、分裂,并且液滴蒸发得以控制。显然,封闭系统才能满足在微流控芯片中进行全自动的生物化学反应的要求。
样本的混匀在生物化学反应中至关重要,可加速微粒的碰撞,在一定程度上促进反应进行。湍流条件下粒子被动扩散是流体混匀的主要机制,然而微尺度下流体的体积流率低、雷诺数小,液体的层流状态难以被改变,使得流体中粒子的主动扩散成为主要的混匀机制。温度和粒子尺寸是影响粒子主动扩散的主要原因,温度越高、粒径越小,主动扩散越快。因此,微全分析系统(μTAS)中生物或化学样本在常温下的混匀所需时间较长,尤其针对于含有蛋白、核酸、细胞等大分子样本,微米尺度下的扩散混匀时间可能长达几分钟甚至几小时。
混匀按照是否需要外界能源可分为被动混匀和主动混匀。为提高微尺度下层流流体的混匀效率,可通过搅拌、震动等方式产生湍流,提高粒子扩散速率,从而提高被动混匀效率;亦可通过将液体剪切为相互间隔的薄层,减小扩散距离提高主动混匀效率。基于以上两种加速混匀的原理,EWOD中的混匀方式可分为以下三种方式:涡流式、移动式、分裂融合式。
涡流式混匀器利用高频交流电在静止的液滴内部产生涡流实现混匀。事实上,电压的频率和幅值增大均能加快混匀速率,但同时会在大液滴附近产生微卫星液滴导致样本体积减小,并且热效应累积导致样本温度上升,这在生物化学反应中通常是不允许的。显然,以上两个因素限制了涡流式混匀器混匀效率。
移动式混匀器通过驱动液滴在直线排列的n块电极上往复运动,或驱动液滴沿某一方向或特定路径在m*n的矩形排列电极上循环运动。但是微尺度下流体的流动可逆性,不合理的路径设计甚至会使经过多次循环后,已经形成多层相互间隔的液滴又恢复到最初不融合状态。更重要的是,该种混匀器所需电极数量较多,增大芯片体积;在液滴移动过程中也增加了交叉污染和芯片表面淤积的风险。
分裂融合式混匀器通过在直线排布的3个连续的电极上,进行反复的液滴分裂——融合,从而达到混匀的目的。该方式混匀所需电极面积有限,并且可避免热效应积累、微卫星液滴产生。研究表明分裂融合式混匀速率较移动式和涡流式有一定优势,尤其是在纵横比较小的封闭系统中。但是目前该种混匀器结构单一,仅在同一方向上进行反复的分裂融合,需要经过多次反复才能实现混匀的效果,所需混匀时间难以满足快速反应的需求。因此,需要通过设计新型分裂融合式混匀器,减少混匀所需的分裂融合次数,提高混匀效率。
发明内容
为了克服上述现有技术的缺点,本发明的目的在于提出了一种封闭EWOD芯片中液滴多维快速混匀方法,实现封闭的EWOD系统中液滴的多维分裂——融合,提高混匀效率。
为了达到上述目的,本发明采取的技术方案为:
一种封闭EWOD芯片中液滴多维快速混匀方法,包括以下步骤:
步骤1,采用液滴多维混匀电极结构,驱动两种不同的液滴样本分别从左右两个进样电极进入,依次经过过渡电极到达融合电极,合并为一个大液滴;
步骤2,在某一方向或者某几个方向上进行液滴的一次分裂;
步骤3,一次分裂结束后,液滴再次回到融合电极合并为一个大液滴;
步骤4,在与一次分裂垂直或者成一定角度的方向上进行二次分裂;
步骤5,分裂完成后,液滴再次在融合电极上合并;
步骤6,重复步骤2-5,直至得到混合均一的溶液;
步骤7,对融合电极下方的出样电极施加高电压,将混匀的液滴移出融合电极。
所述的液滴多维混匀电极结构包含进样电极、过渡电极、分裂电极、融合电极和出样电极,分裂电极和过渡电极有公用部分,各部分电极形状、大小、驱动顺序相互配合,实现EWOD芯片中的多维分裂——融合,进而实现快速混匀。
所述的融合电极为任意多边形,融合电极四周分布有与融合电极相对应的分裂电极,融合电极两侧分布有进样电极,完成不同的液滴从两个方向同步进样;在进样电极和融合电极之间设有过渡电极,过渡电极与分裂电极有公共部分,过渡电极总面积与进样电极相同;在融合电极下方分布有出样电极,实现混匀后的液滴从出样电极输出。
所述的融合电极的左右两侧分布有两个矩形进样电极,两个进样电极中间的16个顶角为45°的等腰三角形电极共同构成融合电极和分裂电极,融合电极是由中心的8个三角形组成的正八边形,分裂电极为分布在融合区外侧的与融合电极完全相同的8个三角形电极;过渡电极由进样电极和融合电极之间的三个小三角形电极构成。
本发明方法的有益效果为:
(1)利用液滴多维混匀电极结构实现液滴多维分裂融合达到混匀的目的,克服了移动式混匀所需电极面积大,易产生交叉污染和表面淤积等问题;相比于涡流式混匀方法,所需电压、频率较小,不会产生微卫星液滴和热量。
(2)采用液滴多维混匀方法不仅能缩短反应时间,并且完善系统的功能,使样本进——结果出的全自动微流控片上反应成为可能。
(3)采用液滴多维混匀电极结构完成混匀,有助于全自动微流控芯片在生物化学领域的推广。
附图说明
图1是本发明方法采用的液滴多维混匀电极结构的示意图。
图2是本发明利用图1液滴多维混匀电极结构进行液滴多维快速混匀示意图,图中阴影表示该电极施加高电压。
具体实施方式
下面结合附图对本发明做详细描述。
参照图1,一种液滴四维混匀芯片结构,包含左右进样电极E1和E2;左右过渡电极F1和F2;融合电极C1-1、C1-2、C1-3、C1-4和C2-1、C2-2、C2-3、C2-4、分裂电极D1-1、D1-2、D1-3、D1-4和D2-1、D2-2、D2-3、D2-4;出样电极T1;进样电极E1和E2为左右两个矩形进样电极;过渡电极F1由三角形电极D1-2、D2-1和一个直角三角电极拼合而成,过渡电极F2由三角形电极D1-4、D2-3和一个直角三角电极拼合而成;三角形电极C1-1、C1-2、C1-3、C1-4和C2-1、C2-2、C2-3、C2-4共同构成融合电极;三角形电极D1-1~D1-4、D2-1~D2-4共同构成分裂电极;所述的三角形电极D1-1、D1-2、D1-3、D1-4、D2-1、D2-2、D2-3、D2-4、C1-1、C1-2、C1-3、C1-4、C2-1、C2-2、C2-3、C2-4是顶角为45°的等腰三角形。各部分电极形状、大小、驱动顺序相互配合,实现EWOD芯片中的多维分裂——融合,实现快速混匀。
参照图2,一种封闭EWOD芯片中液滴多维快速混匀方法,包括以下步骤:
步骤1,采用液滴多维混匀电极结构,驱动两种不同的液滴样本分别从左右两个进样电极E1和E2进入,依次经过过渡电极F1和F2到达融合电极C1-1、C1-2、C1-3、C1-4和C2-1、C2-2、C2-3、C2-4,如图2(a)、(b)、(c)所示,合并为一个大液滴;
步骤2,对分裂电极D1-1~D1-4和融合电极C1-1~C1-4同时施加高电压,完成液滴沿两个相互垂直方向的一次分裂,如图2(d)所示;
步骤3,对融合电极C1-1~C1-4和C2-1~C2-4同时施加高电压,使液滴再次融合,如图2(e)所示;
步骤4,对分裂电极D2-1~D2-4和融合电极C2-1~C2-4施加高电压,完成液滴沿另外两个相互垂直方向的二次分裂,如图2(f)所示;
步骤5,对融合电极C1-1~C1-4和C2-1~C2-4同施加高电压,使液滴第三次融合,如图2(g)所示;
步骤6,重复步骤2-5,直至得到混合均一的溶液;
步骤7,对出样电极T1施加高电压,如图2(h)所示,将混匀后的液滴移出融合电极。
本实施例经过一次分裂和二次分裂可实现8个方向的液滴分裂——融合,有效减少混匀所需的分裂——融合次数;各部分电极形状、大小、驱动顺序相互配合,可实现液滴的最佳混匀效果。
本发明方法利用液滴的分裂融合混匀的原理,通过液滴多维混匀电极结构,使液滴可沿相互垂直或程一定角度的多个方向进行两次分裂,实现二维、四维、多维的液滴分裂后融合,实现封闭的EWOD系统中液滴的快速混匀。
Claims (4)
1.一种封闭EWOD芯片中液滴多维快速混匀方法,其特征在于,包括以下步骤:
步骤1,采用液滴多维混匀电极结构,驱动两种不同的液滴样本分别从左右两个进样电极进入,依次经过过渡电极到达融合电极,合并为一个大液滴;
步骤2,在某一方向或者某几个方向上进行液滴的一次分裂;
步骤3,一次分裂结束后,液滴再次回到融合电极合并为一个大液滴;
步骤4,在与一次分裂成一定角度的方向上进行二次分裂;
步骤5,分裂完成后,液滴再次在融合电极上合并;
步骤6,重复步骤2-5,直至得到混合均一的溶液;
步骤7,对融合电极下方的出样电极施加高电压,将混匀的液滴移出融合电极。
2.根据权利要求1所述的一种封闭EWOD芯片中液滴多维快速混匀方法,其特征在于:所述的液滴多维混匀电极结构包含进样电极、过渡电极、分裂电极、融合电极和出样电极,分裂电极和过渡电极有公用部分,各部分电极形状、大小、驱动顺序相互配合,实现EWOD芯片中的多维分裂——融合,进而实现快速混匀。
3.根据权利要求2所述的一种封闭EWOD芯片中液滴多维快速混匀方法,其特征在于:所述的融合电极为任意多边形,融合电极四周分布有与融合电极相对应的分裂电极,融合电极两侧分布有进样电极,完成不同的液滴从两个方向同步进样;在进样电极和融合电极之间设有过渡电极,过渡电极与分裂电极有公共部分,过渡电极总面积与进样电极相同;在融合电极下方分布有出样电极,实现混匀后的液滴从出样电极输出。
4.根据权利要求2所述的一种封闭EWOD芯片中液滴多维快速混匀方法,其特征在于:所述的融合电极的左右两侧分布有两个矩形进样电极,两个进样电极中间的16个顶角为45°的等腰三角形电极共同构成融合电极和分裂电极,融合电极是由中心的8个三角形组成的正八边形,分裂电极为分布在融合区外侧的与融合电极完全相同的8个三角形电极;过渡电极由进样电极和融合电极之间的三个小三角形电极构成。
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