Name: one-step approach to fabricating polydimethylsiloxane microfluidic channels of different geometric sections by sequential wet etching processes
Uploaded: 2018-09-13T14:00:00.000+00:00
Duration: 8 min 31 s
Description: Watch this Scientific Journal Video about One-Step Approach to Fabricating Polydimethylsiloxane Microfluidic Channels of Different Geometric Sections by Sequential Wet Etching Processes at JoVE.com

作者感谢台湾国家卫生研究院 (IRG) (EX106-10523EI)、台湾省科技部 (最 104-2218-032-004、104-2221) 在台湾提供的支持。E-001-015-MY3, 105-2221-001-002-MY2, 105-2221-032-006, 106-2221-032-018-MY2), 和研究院职业发展奖。作者感谢恒华许校对稿件。

1. 单层通道布局微流控装置的制作
注: 本文采用3软光刻法制作了微流控器件, 以演示如何制作不同断面的通道。
<ol><li>
用设计的拓扑特征创建一层聚硅烷的主模
	<ol>
<li>为单个蚀刻工艺或按顺序进行蚀刻, 设计了一个在该层上的通道布局。</li>
		<li>利用计算机辅助绘图程序, 勾勒出所设计的聚硅烷层的反向拓扑特征。</li>
		<li>将草绘文件传送到光刻设备, 以获得在透明24上打印的通道布局的高精度反向拓扑特征的图案化光掩模。</li>
		<li>使用异丙醇 (2-丙醇 (IPA), ≥ 99.9%), 丙酮 (Propan-2-one, ≥ 99.5%), 和缓冲氧化物蚀刻 (教委, NH4F: HF (v/v) = 6:1) 在一个4英寸的硅片表面, 以消除任何灰尘或残余物, 并避免污染物。</li>
		<li>用大约500毫升的去离子水清洗硅片进行最后的抛光, 然后用氮气干燥冲洗过的晶片。</li>
		<li>在晶片上放置一个20克左右的负色调光刻胶。然后旋转涂层的硅片在十五年代和2000转每分钟 500 rpm 三十年代生产的光刻胶层约75µm 在厚度。 注: 根据用户手册25,26, 不同的产品编号和不同的自旋涂层、烘烤和开发条件, 可以实现各种光刻胶厚度的光刻胶。</li>
		<li>软烤晶圆片加热在热板上65°c 3 分钟, 然后在95°c 9 分钟。</li>
		<li>将晶片放入光掩模光刻机中, 并将步骤1.1.3 中的图案透明度作为掩码。</li>
		<li>在光刻机中, 应用紫外线 (UV) 光在300兆焦耳/厘米2 , 以暴露晶片覆盖的透明度。</li>
		<li>紫外线照射后, 将硅片放在65摄氏度的热板上, 2 分钟, 然后在95摄氏度为7分钟后曝光烘烤 (PEB)。</li>
		<li>继 PEB 后, 强烈鼓动晶片浸入负色调的光刻胶显影液中, 或将浸入式晶片置于超声波浴中 (37 赫, 有效功率为 180 W) 为7分钟。</li>
		<li>再次用异丙醇清洗整个晶片, 以消除任何残留在晶片表面的显影液。</li>
		<li>为了防止不期望的粘合, silanize 硅片的表面, 将硅片与100µL 硅烷 (1h, 1H, 2h, 2hperfluorooctyl 烷) 一起放在干燥的6厘米培养皿中。</li>
		<li>将干燥连接到真空泵, 并将真空压力设置为 760 mmHg。</li>
		<li>接着, 把泵打开15分钟, 关掉它, 然后把晶片放在干燥的真空中休息30分钟。 注意: 蒸发的硅烷对人类极其有害;因此, 整个晶片表面钝化必须在通风罩中进行。</li>
		<li>提取硅烷化晶圆片, 该晶片正在进行表面钝化。将晶片固定在15厘米培养皿中以供进一步使用。 注: 该图案晶圆片已准备好用作模具, 可将设计的通道布局与该材料反向复制。</li>
	</ol>
</li>
	<li>
在模具上复制反向拓扑, 制作出了基于该电路的通道布局
	<ol>
<li>将基体 (单体) 与相应的催化剂 (固化剂) 放在10:1 的体积比上, 变成一个干净的单用塑料杯。</li>
		<li>使用动力搅拌器均匀地混合1.2.1 预聚体混合物 (从步进法)。</li>
		<li>把杯子放在与真空泵相连的干燥上60分钟, 以除去该混合物中的任何陷泡气泡。</li>
		<li>将20克 (2 节) 或8克 (3 节) 倒入主模具 (步骤 1.1) 的顶部, 与设计的通道布局的反向拓扑特征混合, 然后通过使用 t 来消除任何可能的气泡嵌入到该材料中。他干燥 (60 分钟)。</li>
		<li>将以60°c 为4小时的混合材料放入烤箱, 以固化硅基液体预聚物。</li>
		<li>在将晶片冷却到室温约20分钟后, 用手术刀和镊子将固化后的硅烷从模具中分离出来。</li>
		<li>用手术刀将分离后的一层 (2 或 2 x 7.5 厘米2 ) 的区域 (约为 6 x 6 厘米2 ) 定制为部分。</li>
		<li>使用直径为1.5 毫米的活检打孔创建通道访问端口 (入口和插座)。 注: 入口和插座的数量和位置是根据蚀刻工艺设计的, 用于制造特定的微流控通道。</li>
		<li>将30克的硅烷预聚物倒入培养皿中, 然后通过使用干燥 (60 分钟) 消除在该材料中嵌入的任何可能的气泡。</li>
		<li>将培养皿携带在60摄氏度的烤箱中, 以4多小时的温度来治疗液体预聚体材料。</li>
		<li>在将培养皿冷却到室温约20分钟后, 用手术刀和镊子将已固化的。</li>
		<li>使用手术刀, 在不带任何特征的情况下, 将独立的......... 6 x 6 厘米2 2 或 2 x 7.5 厘米2条的尺寸。</li>
		<li>在四十年代 90 W 的表面处理机上, 用设计的通道布局和不带任何特征的 1.2.7, 激活两层的表面。</li>
		<li>通过在氧等离子体表面活化后, 在处理过的表面之间进行接触, 来粘合2层。然后, 在烤箱中将粘合的60摄氏度保持在30分钟以上。 注: 在烤箱中, 不存在将粘合的聚硅烷层留在上面的时间限制。</li>
		<li>在2个粘合后的单层冷却后, 将多余的材料从预制装置中修剪出来, 供以后的实验设备用。</li>
	</ol>
</li>
</ol>2. 用一步法制备不同断面的微流控流体通道
注: 为了表征其湿蚀刻速率, 建议利用单层和直通道矩形形状的微流控装置来识别与某些实验设置相对应的特定蚀刻速率。
<ol><li>
硅烷湿法蚀刻的实验表征
	<ol>
<li>用 1-甲基-2-咯烷酮 (NMP) 混合四氟铵氟化物 (TBAF, 1 M 溶液), 用 v: v = 1:10, 制备蚀刻溶液。 注: NMP 能有效溶解腐蚀剂诱导的化学残留。一般情况下, NMP 材料的肿胀略有上升, 而该微流控芯片仍能保持其形状、体积和密封条件。</li>
		<li>将混合 TBAF/NMP 腐蚀剂与不锈钢钝针 (16 克) 连接在一起的10毫升注射器中。</li>
		<li>在通道中设置注射器泵作为压力驱动流体的控制器。</li>
		<li>将用蚀刻溶液填充的注射器的钝针连接到上述简单设备的通道端口, 并将各自的端口从出口油管引导到废物容器, 如图 1所示。</li>
		<li>运行注射器泵携带注射器含有混合 TBAF/NMP 蚀刻解决方案, 以150µL/分钟的流量率, 以表征该法的湿蚀刻。</li>
		<li>使用光亮场显微观察, 确保沿流方向的蚀刻通道宽度一致, 从而确认腐蚀剂的体积混合比和蚀刻流速是足够的。</li>
		<li>捕获在反相显微镜下的通道剖面的时间序列图像, 并在其蚀刻过程中使用4X 放大倍数。</li>
		<li>通过在图像处理程序的2D 分析中应用基本测量函数对存储图像进行分析, 收集了在材料湿法蚀刻过程中通道宽度的时间序列。</li>
		<li>通过图 2所示的等式评估时间序列蚀刻速率, 该公式在50% 的通道宽度变化 (ΔW /2) 的持续时间内进行.</li>
		<li>对所收集的数据点进行线性回归, 估计混合 TBAF/NMP 腐蚀剂的总蚀刻率, 并以1:10 的具体体积混合比为原料, 如图 2所示。</li>
	</ol>
</li>
	<li>
用于制造不同几何剖面微流控通道的连续湿法蚀刻
	<ol>
<li>设计了单层蚀刻通道布局的排列方式, 为相应的蚀刻过程依次提供服务, 使图 3中所示的不同横截面形状的特定通道类型能够被制造出来。</li>
		<li>按照步骤 2.1.1 2.1.7 中描述的过程, 对其湿蚀刻方法进行操作。 注: 流量设置为 50 ul/分钟。</li>
		<li>当 TBAF/NMP 腐蚀剂在流动时, 检查显微镜下的蚀刻通道, 看看是否存在重大问题, 如明显的气泡量, 残余的几个化学残留的腐蚀剂诱导, 泄漏的腐蚀剂,或腐蚀剂在倾斜的平面上的流动。</li>
		<li>通过倒置显微镜观察微流控通道壁厚变化, 并对湿法蚀刻过程进行时间测量, 以确保正确的通道几何形状。</li>
	</ol>
</li>
</ol>3. 微流控搅拌机的设计
注: 介绍了一种能有效混合2种不同流体的微流控混合器的设计, 展示了微流控通道与各断面的优势应用。
<ol><li>
不同通道段微流控混频器的研制
	<ol>
<li>用软光刻复制器成型技术 (2 节) 制作图 4所示的单层微流控芯片。</li>
		<li>在单层微流控通道布局中, 介绍了 TBAF/NMP 蚀刻解决方案, 按照步骤2.1.1 中描述的过程, 从标记为 "插座" 的端口在图 4中的20µL/分钟流速。</li>
		<li>在显微镜下观察微流控通道壁厚变化, 并对湿法蚀刻过程进行时间测量, 以确保图 5所示的正确的通道几何。</li>
	</ol>
</li>
	<li>
微流控混合机的实验表征
	<ol>
<li>在一个交替模式中实现了不同形状截面的微流控通道后, 泵浦2种不同的流体, 其中有50µg/毫升浓度的荧光素钠盐溶液, 在20µL/分钟内将蒸馏水分成2个不同的通道。流量。</li>
		<li>在上图中以 A、B、C 和 D 为标记的位置, 在2混合器 (在蚀刻前) 和不同的几何截面 (舒瑞普2小时后) 下, 将该通道的荧光显微镜图像分别 (图 6)。 注: 采用荧光显微镜图像, 当稳定流发生时, 在5分钟的时间点, 计数从混合通过混合器通道的开始时刻。</li>
		<li>利用图像处理程序对捕获的荧光图像进行分析, 以估计在以下等式27中由混合残余 (MR, 0.5 = 纯, 0 = 完全混合) 定义的相应混合效率数.28: <img alt="Equation" src="/files/ftp_upload/57868/57868eq1v2.jpg"> 这里 t是蚀刻时间, L是通道宽度在某一位置的兴趣, S是在该位置的通道上的线段, 并 我是荧光强度分布在S t。</li>
		<li>将荧光强度分布在通道上, 在标记为 A、B、C 和 D 的位置上, 分别为2混合器 (在蚀刻前) 和不同的几何截面 (舒瑞普2小时后)。估计图 6所示的相应 MR。</li>
	</ol>
</li>
</ol>

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C., Kurabayashi, K. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=A+Single-Layer+PDMS-On-Silicon+Hybrid+Microactuator+with+Multi-Axis+Out-Of-Plane+Motion+Capabilities-Part+II:+Fabrication+and+Characterization.">A Single-Layer PDMS-On-Silicon Hybrid Microactuator with Multi-Axis Out-Of-Plane Motion Capabilities-Part II: Fabrication and Characterization.</a> Journal of Microelectromechanical Systems. 14, 558-566 (2005).</li><li>Chen, W., Lam, R. H. W., Fu, J. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Photolithographic+Surface+Micromachining+of+Polydimethylsiloxane+(PDMS).">Photolithographic Surface Micromachining of Polydimethylsiloxane (PDMS).</a> Lab on a Chip. 12, 391-395 (2012).</li><li>Balakrisnan, B., Patil, S., Smela, E. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Patterning+PDMS+Using+a+Combination+of+Wet+and+Dry+Etching.">Patterning PDMS Using a Combination of Wet and Dry Etching.</a> Journal of Micromechanics and Microengineering. 19, 047002 (2009).</li><li>Takayama, S., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Topographical+Micropatterning+of+Poly(dimethylsiloxane)+Using+Laminar+Flows+of+Liquids+in+Capillaries.">Topographical Micropatterning of Poly(dimethylsiloxane) Using Laminar Flows of Liquids in Capillaries.</a> Advanced Materials. 13, 570-574 (2001).</li><li>Friend, J., Yeo, L. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Fabrication+of+Microfluidic+Devices+Using+Polydimethylsiloxane.">Fabrication of Microfluidic Devices Using Polydimethylsiloxane.</a> Biomicrofluidics. 4, 026502 (2010).</li><li>. NANO SU-8 2000 Negative Tone Photoresist formulations 2002-2025 Available from: <a target="_blank" href="https://www.seas.upenn.edu/~nanosop/documents/SU8_2002-2025.pdf">https://www.seas.upenn.edu/~nanosop/documents/SU8_2002-2025.pdf</a> (2000)</li><li>. NANO SU-8 2000 Negative Tone Photoresist formulations 2035-2100 Available from: <a target="_blank" href="https://www.seas.upenn.edu/~nanosop/documents/SU8_2035-2100.pdf">https://www.seas.upenn.edu/~nanosop/documents/SU8_2035-2100.pdf</a> (2000)</li><li>Hardt, S., Sch&#246;nfeld, F. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Laminar+Mixing+in+Different+Interdigital+Micromixers:+II.+Numerical+Simulations.">Laminar Mixing in Different Interdigital Micromixers: II. Numerical Simulations.</a> AIChE Journal. 49, 578-584 (2003).</li><li>Hessel, V., L&#246;we, H., Sch&#246;nfeld, F. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Micromixers-A+Review+on+Passive+and+Active+Mixing+Principles.">Micromixers-A Review on Passive and Active Mixing Principles.</a> Chemical Engineering Science. 60, 2479-2501 (2005).</li><li>Damiati, S., Kompella, U., Damiati, S., Kodzius, R. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Microfluidic+Devices+for+Drug+Delivery+Systems+and+Drug+Screening.">Microfluidic Devices for Drug Delivery Systems and Drug Screening.</a> Genes. 9, 103 (2018).</li><li>Wang, C. -. K., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Single+Step+Sequential+Polydimethylsiloxane+Wet+Etching+to+Fabricate+a+Microfluidic+Channel+with+Various+Cross-Sectional+Geometries.">Single Step Sequential Polydimethylsiloxane Wet Etching to Fabricate a Microfluidic Channel with Various Cross-Sectional Geometries.</a> Journal of Micromechanics and Microengineering. 27, 115003 (2017).</li></ol>

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在过去的几十年中, 微流体为化学和生物医学研究的实验平台提供了有希望的手段, 可以系统地构建1、2、3、4、 5。这些平台还展示了他们的能力, 通过体外细胞研究6,7,在生理微环境条件下研究体内的几种细胞...

微流控技术在过去的几十年中引起了人们的注意, 因为它们在各种生物医学和化学研究和应用中具有内在的优势。目前有几种用于构造微流控芯片的材料使用方法, 如聚合物、陶瓷和硅材料。根据我们的知识, 在微流控材料中, 由于其对各种微流体的研究和应用, 包括其光学和生物兼容性与粒子, 因此, 它是最常见的一种材料。液体和非常小活有机体1,2,3,4,5。此外, 通过应用这种聚合物基微流控器件 10, 可调整其表面化学和结构力学性能, 以促进 microelectromechanical 和 mechanobiological 研究, 11,12。对于采用设计的通道模式制造微流控器件, 通常采用软光刻复制模塑方法, 利用其相应的主模具来创建微流控通道, 其组成为光刻图案光刻胶层和硅片基板12。由于采用了带有图案光刻胶层的硅片的成型方法的性质, 微流控通道通常具有相同高度的矩形形状的正截面。
最近, 研究人员在生物医学研究方面取得了重大进展, 例如, 利用 hydrophoresis、分离血浆和丰富白细胞的途径对微粒和细胞进行分类, 并将微流控芯片应用于不同的高度或几何部分6,7,8,9。通过自定义不同几何剖面的通道, 实现了生物医学应用中微流体的分类和分离功能。通过制作具有不同高度或非矩形截面的特殊表面模式的主模具, 对具有各几何特征截面的微流控通道进行了若干研究。这些关于模具制造的研究包括多步光刻、光刻胶回流和灰阶光刻13、14、15等技术。不可避免的是, 现有的技术包括精心制作的光掩膜或在多步制造过程中的精确对准, 这可能大大提高了相应制造微流控通道的复杂性水平。到目前为止, 对不同断面微流控通道的单步法制造工艺进行了几次尝试, 但各自的技术高度限制在16通道的特定横断面形状上。
在过去的两年中, 除了用不同的截面制造新的微流控流体通道的成型方法外, 采用几何特征的模式的蚀刻技术已成为各种选择的制造方式。微流控应用程序。例如, 微流体的湿法蚀刻是利用多层的聚硅烷键合来构建一种具有重组器官级肺功能的气动驱动细胞培养装置的17。采用 microwells 的湿法蚀刻技术, 利用计算机辅助控制系统加工制造3D 敷微针阵列18的外圆管, 对其进行了制备。在微机电致动器19、20中, 采用了聚硅烷干法蚀刻, 使其作为微观结构的组成部分。通过21的干法蚀刻工艺, 设计出孔隙布局的多孔型聚合物膜。湿式和干法蚀刻技术都可以集成到图案为22的几何形状。
然而, 由于其在微流控加工中的固有局限性, 形成复杂断面形状的聚硅烷通道结构的蚀刻技术还没有得到普遍应用。首先, 在建立不同断面微流控流体通道的化学物质层流法的基础上, 对其湿蚀刻技术进行了研究, 但由于其基本特征, 后续通道段的形成仍受到限制。各向同性化学蚀刻工艺23。此外, 虽然似乎有合理的空间, 以控制通道剖面几何在微流体制造使用了20, 所需的蚀刻时间通常是太长 (在小时)生产微流控芯片的实用。此外, 该材料与相应的屏蔽光刻胶层之间的蚀刻选择性一般都很低, 因此, 这些通道的蚀刻深度是不可接受的20。
本文提出了一种单步法制备不同几何横截面微流控通道的方法 (以下简称舒瑞普)。舒瑞普从单层通道的微流控芯片开始。通过对各种通道的布局设计, 通过顺序蚀刻工艺, 制作出不同几何截面的微流控通道。顺序蚀刻只需要一个蚀刻, 被引入到计划的单层布局的具体渠道嵌入在该材料。与传统的舒瑞普制造工艺相比, 该方法只需要一个进一步的步骤来制造非矩形截面或不同高度的微流控通道。所提出的舒瑞普提供了一个简单而简便的方法, 制造微流控通道的各个部分沿流动方向, 这可以大大简化上述方法的过程。

<table><tbody><tr><td>1-Methyl-2-Pyrrolidinone</td><td>Tedia, Fairfield, OH</td><td>ME-1962</td><td>NMP</td></tr><tr><td>10 ml Syringe</td><td>Becton-Dickinson, Franklin Lakes, NJ</td><td>302151</td><td></td></tr><tr><td>150 mm Petri dish</td><td>Dogger Science</td><td>DP-43151</td><td></td></tr><tr><td>1H,1H,2H,2H- Perfluorooctyltrichlorosilane</td><td>Alfa Aesar, Ward Hill, MA</td><td>L16606</td><td>97 % silane&amp;nbsp;</td></tr><tr><td>4&#039;&#039; Silicon Dummy Wafer</td><td>Wollemi Technical, Taoyuan, Taiwan</td><td>-</td><td></td></tr><tr><td>Acetone</td><td>ECHO Chemical, Miaoli, Taiwan</td><td>AH3102-000000-72EC</td><td></td></tr><tr><td>AG Double Expose Mask Aligner</td><td>M&amp;amp;R Nano Technology, Taoyuan, Taiwan</td><td>AG500-4D-D-V-S-H</td><td></td></tr><tr><td>Biopsy Punch</td><td>Miltex, Plainsboro, NJ</td><td>33-31</td><td></td></tr><tr><td>Blunt Needle</td><td>Jensen Global, Santa Barbara, CA</td><td>Gauge 16</td><td></td></tr><tr><td>Buffered Oxide Etch</td><td>ECHO Chemical, Miaoli, Taiwan</td><td>PH3101-000000-72EC</td><td></td></tr><tr><td>Desicattor</td><td>A-VAC Industries, Anaheim, CA</td><td>35.10001.01</td><td></td></tr><tr><td>Fluorescein Sodium Salt Water</td><td>Sigma-Aldrich Co., St Louis, MO</td><td>F6300</td><td></td></tr><tr><td>ImageJ</td><td>National Institutes of Health, Bethesda, MD</td><td>Ver. 1.51</td><td>Imaging Processing Program&amp;nbsp;</td></tr><tr><td>Inverted Fluorescence Microscope&amp;nbsp;</td><td>Leica Microsystems, Wetzlar, Germany</td><td>DMI 6000 B</td><td></td></tr><tr><td>Isopropyl Alcohol (IPA)</td><td>ECHO Chemical, Miaoli, Taiwan</td><td>CMOS112-00000-72EC</td><td></td></tr><tr><td>Leica Application Suite&amp;nbsp;</td><td>Leica Microsystems GmbH</td><td>LAS X</td><td></td></tr><tr><td>MATLAB</td><td>MathWorks, Natick, MA</td><td>R2015b</td><td>Programming for MR evaluation</td></tr><tr><td>Mechanical Convention Oven</td><td>ThermoFisher Scientific,Waltham, MA</td><td>Lindberg Blue M MO1450C</td><td></td></tr><tr><td>Plasma Tretment System</td><td>Nordson MARCH, Concord CA</td><td>PX-250</td><td>Oxygen plasma surface treatment</td></tr><tr><td>Polydimehtylsiloxane (PDMS)&amp;nbsp;</td><td>Dow Corning, Midland, MI</td><td>SYLGARD 184</td><td></td></tr><tr><td>Polyethylene Tubing</td><td>Becton-Dickinson and Company, Sparks, MD</td><td>427446</td><td>PE 205, 10&#039;</td></tr><tr><td>Spin Coater</td><td>ELS Technology, Hsinchu, Taiwan</td><td>ELS 306MA</td><td></td></tr><tr><td>Negative Tone Photoresist&amp;nbsp;</td><td>MicroChem, Westborough, MA</td><td>SU-8 2050</td><td></td></tr><tr><td>Negative Tone Photoresist Developer</td><td>MicroChem, Westborough, MA</td><td>Y020100</td><td>SU-8 Developer</td></tr><tr><td>Surgical Blade</td><td>Feather, Osaka, Japan</td><td>5005093</td><td>PDMS cutting</td></tr><tr><td>Syringe Pump</td><td>Chemyx, Houston, TX</td><td>Fusion 400</td><td></td></tr><tr><td>Tetra-n-butylammonium Fluoride (TBAF)</td><td>Alfa Aesar, Ward Hill, MA</td><td>A10588</td><td></td></tr></tbody></table>

one-step approach to fabricating polydimethylsiloxane microfluidic channels of different geometric sections by sequential wet etching processes

烷的材料被大量利用来制造微流控器件, 采用软光刻复制的成型技术。在许多生物医学和化学应用 (如细胞培养、生物传感、化学合成和液体处理) 中, 对微流控器件的特定功能和综合性能而言, 定制的渠道布局设计是必要的。由于采用了以光刻为主模的光刻胶层的硅晶片的成型方法的性质, 微流控通道通常具有相同高度的矩形形状的正截面。通常, 具有多个高度或不同几何截面的通道设计为具有特定功能, 并可在各种微流控应用程序中执行 (例如, hydrophoresis 用于对粒子进行排序, 并在连续流中用于分离血细胞6,7,8,9)。因此, 通过多步骤的方法, 如光刻, 采用不同的光刻胶层和组合, 在各断面的施工渠道进行了大量的努力。然而, 这种多步骤方法通常涉及繁琐的程序和广泛的工具。此外, 捏造的设备可能不会持续执行, 结果实验数据可能是不可预知的。在这里, 为直接制造不同几何横截面的微流控通道提供了一步法, 该方法将蚀刻引入计划的单层布局通道中。嵌入式材料。与现有的不同几何形状的微流控流体通道制造方法相比, 所研制的一步法可显著简化非矩形截面或不同高度的通道制作过程。因此, 该技术是构造复杂微流控通道的一种方法, 为创新微流控系统的发展提供了一种制造方案。

近年来, 大量研究了通过光刻复制13、14、15和聚硅烷蚀刻技术, 对不同断面通道的微流控装置进行制作;17,18,19,20,21,22. 然而, 在制造作业16</su...

Watch this Scientific Journal Video about One-Step Approach to Fabricating Polydimethylsiloxane Microfluidic Channels of Different Geometric Sections by Sequential Wet Etching Processes at JoVE.com

One-Step Approach to Fabricating Polydimethylsiloxane Microfluidic Channels of Different Geometric Sections by Sequential Wet Etching Processes

连续湿法刻蚀法制作不同几何断面烷微流控通道的一步法

对烷微流控器件中嵌入的非矩形截面通道的制作, 有几种方法可供选择。其中大部分涉及多步骤制造和广泛的对准。本文介绍了用烷连续湿法刻蚀法制作不同几何剖面微流控通道的一步法。

Polydimethylsiloxane (PDMS) materials are substantially exploited to fabricate microfluidic devices by using soft lithography replica molding techniques. ...

one-step-approach-to-fabricating-polydimethylsiloxane-microfluidic

Research

JoVE Journal

Engineering

9.7K 次观看.  Academia Sinica. 对烷微流控器件中嵌入的非矩形截面通道的制作, 有几种方法可供选择。其中大部分涉及多步骤制造和广泛的对准。本文介绍了用烷连续湿法刻蚀法制作不同几何剖面微流控通道的一步法。

视频: One-Step Approach to Fabricating Polydimethylsiloxane Microfluidic Channels of Different Geometric Sections by Sequential Wet Etching Processes

Microfluidic Mixers for Studying Protein Folding

The process by which a protein folds into its native conformation is highly relevant to biology and human health yet still poorly understood. One reason for this is that folding takes place over a wide range of timescales, from nanoseconds to seconds or longer, depending on the protein1. Conventional stopped-flow mixers have allowed measurement of folding kinetics starting at about 1 ms. We have recently developed a microfluidic mixer that dilutes denaturant ~100-fold in ~8 &mu;s2. Unlike a stopped-flow mixer, this mixer operates in the laminar flow regime in which turbulence does not occur. The absence of turbulence allows precise numeric simulation of all flows within the mixer with excellent agreement to experiment3-4.
Laminar flow is achieved for Reynolds numbers Re &le;100. For aqueous solutions, this requires micron scale geometries. We use a hard substrate, such as silicon or fused silica, to make channels 5-10 &mu;m wide and 10 &mu;m deep (See Figure 1). The smallest dimensions, at the entrance to the mixing region, are on the order of 1 &mu;m in size. The chip is sealed with a thin glass or fused silica coverslip for optical access. Typical total linear flow rates are ~1 m/s, yielding Re~10, but the protein consumption is only ~0.5 nL/s or 1.8 &mu;L/hr. Protein concentration depends on the detection method: For tryptophan fluorescence the typical concentration is 100 &mu;M (for 1 Trp/protein) and for FRET the typical concentration is ~100 nM.
The folding process is initiated by rapid dilution of denaturant from 6 M to 0.06 M guanidine hydrochloride. The protein in high denaturant flows down a central channel and is met on either side at the mixing region by buffer without denaturant moving ~100 times faster (see Figure 2). This geometry causes rapid constriction of the protein flow into a narrow jet ~100 nm wide. Diffusion of the light denaturant molecules is very rapid, while diffusion of the heavy protein molecules is much slower, diffusing less than 1 &mu;m in 1 ms. The difference in diffusion constant of the denaturant and the protein results in rapid dilution of the denaturant from the protein stream, reducing the effective concentration of the denaturant around the protein. The protein jet flows at a constant rate down the observation channel and fluorescence of the protein during folding can be observed using a scanning confocal microscope5.

In this work we explain the fabrication and use of a microfluidic mixer capable of mixing two solutions in ~8 &mu;s. We also demonstrate the use of these mixers with spectroscopic detection using UV fluorescence and fluorescence resonance energy transfer (FRET).

研究蛋白质折叠的微流体混合器

The process by which a protein folds into its native conformation is highly relevant to biology and human health yet still poorly understood. One reason ...

科研

生物工程

Fabrication of the Thermoplastic Microfluidic Channels

In our lab, we have successfully isolated nucleic acids directly from microliter and submicroliter volumes of human blood, urine and stool using polymer/nanoparticle composite microscale lysis and solid phase extraction columns. The recovered samples are concentrated, small volume samples that are PCRable, without any additional cleanup. Here, we demonstrate how to fabricate thermoplastic microfluidic chips using hot embossing and heat sealing. Then, we demonstrate how to use in situ light directed surface grafting and polymerization through the sealed chip to form the composite solid phase columns. We demonstrate grafting and polymerization of a carbon nanotube/polymer composite column for bacterial cell lysis. We then show the lysis process followed by solid phase extraction of nucleic acids from the sample on chip using a silica/polymer composite column. The attached protocols contain detailed instructions on how to make both lysis and solid phase extraction columns.

Here we demonstrate how to fabricate thermoplastic microfluidic chips using hot embossing and heat sealing. Then we demonstrate how to use in situ light directed surface grafting and polymerization through the sealed chip to form the composite solid phase columns.

制备热塑性微流体通道

In our lab, we have successfully isolated nucleic acids directly from microliter and submicroliter volumes of human blood, urine and stool using ...

生物学

Procedure for the Development of Multi-depth Circular Cross-sectional Endothelialized Microchannels-on-a-chip

Efforts have been focused on developing in vitro assays for the study of microvessels because in vivo animal studies are more time-consuming, expensive, and observation and quantification are very challenging. However, conventional in vitro microvessel assays have limitations when representing in vivo microvessels with respect to three-dimensional (3D) geometry and providing continuous fluid flow. Using a combination of photolithographic reflowable photoresist technique, soft lithography, and microfluidics, we have developed a multi-depth circular cross-sectional endothelialized microchannels-on-a-chip, which mimics the 3D geometry of in vivo microvessels and runs under controlled continuous perfusion flow. A positive reflowable photoresist was used to fabricate a master mold with a semicircular cross-sectional microchannel network. By the alignment and bonding of the two polydimethylsiloxane (PDMS) microchannels replicated from the master mold, a cylindrical microchannel network was created. The diameters of the microchannels can be well controlled. In addition, primary human umbilical vein endothelial cells (HUVECs) seeded inside the chip showed that the cells lined the inner surface of the microchannels under controlled perfusion lasting for a time period between 4 days to 2 weeks.

A microchannels-on-a-chip platform was developed by the combination of photolithographic reflowable photoresist technique, soft lithography, and microfluidics. The endothelialized microchannels platform mimics the three-dimensional (3D) geometry of in vivo microvessels, runs under controlled continuous perfusion flow, allows for high-quality and real-time imaging&#160;and can be applied for microvascular research.

发展多深的圆形横截面微内皮化的一个芯片的程序

Efforts have been focused on developing in vitro assays for the study of microvessels because in vivo animal studies are more time-consuming, expensive, ...

Microfluidic Fabrication of Polymeric and Biohybrid Fibers with Predesigned Size and Shape

A &#8220;sheath&#8221; fluid passing through a microfluidic channel at low Reynolds number can be directed around another &#8220;core&#8221; stream and used to dictate the shape as well as the diameter of a core stream.&#160;Grooves in the top and bottom of a microfluidic channel were designed to direct the sheath fluid and shape the core fluid.&#160;By matching the viscosity and hydrophilicity of the sheath and core fluids, the interfacial effects are minimized and complex fluid shapes can be formed.&#160;Controlling the relative flow rates of the sheath and core fluids determines the cross-sectional area of the core fluid.&#160;Fibers have been produced with sizes ranging from 300 nm to ~1 mm, and fiber cross-sections can be round, flat, square, or complex as in the case with double anchor fibers. Polymerization of the core fluid downstream from the shaping region solidifies the fibers.&#160;Photoinitiated click chemistries are well suited for rapid polymerization of the core fluid by irradiation with ultraviolet light.&#160;Fibers with a wide variety of shapes have been produced from a list of polymers including liquid crystals, poly(methylmethacrylate), thiol-ene and thiol-yne resins, polyethylene glycol, and hydrogel derivatives. Minimal shear during the shaping process and mild polymerization conditions also makes the fabrication process well suited for encapsulation of cells and other biological components.

Two adjacent fluids passing through a grooved microfluidic channel can be directed to form a sheath around a prepolymer core; thereby&#160;determining both shape and cross-section. Photoinitiated polymerization, such as thiol click chemistry, is well suited for rapidly solidifying the core fluid into a microfiber with predetermined size and shape.

预设计尺寸和形状的聚合物纤维和生物贿赂纤维的微流体制造

A &#8220;sheath&#8221; fluid passing through a microfluidic channel at low Reynolds number can be directed around another &#8220;core&#8221; stream and ...

Generation of Size-controlled Poly (ethylene Glycol) Diacrylate Droplets via Semi-3-Dimensional Flow Focusing Microfluidic Devices

Uniform and size-controllable poly (ethylene glycol) diacrylate (PEGDA) droplets could be produced via the flow focusing process in a microfluidic device. This paper proposes a semi-three-dimensional (semi-3D) flow-focusing microfluidic chip for droplet formation. The polydimethylsiloxane (PDMS) chip was fabricated using the multi-layer soft lithography method. Hexadecane containing surfactant was used as the continuous phase, and PEGDA with the ultraviolet (UV) photo-initiator was the dispersed phase. Surfactants allowed the local surface tension to drop and formed a more cusped tip which promoted breaking into tiny micro-droplets. As the pressure of dispersed phase was constant, the size of droplets became smaller with increasing continuous phase pressure before dispersed phase flow was broken off. As a result, droplets with size variation from 1 &#181;m to 80 &#181;m in diameter could be selectively achieved by changing the pressure ratio in two inlet channels, and the average coefficient of variation was estimated to be below 7%. Furthermore, droplets could turn into micro-beads by UV exposure for photo-polymerization. Conjugating biomolecules on such micro-beads surface have many potential applications in the fields of biology and chemistry.

Generation of Size-controlled Poly ethylene Glycol Diacrylate Droplets via Semi-3-Dimensional Flow Focusing Microfluidic Devices

Here, we present a protocol to illustrate the fabrication processes and verifying experiments of a semi-three-dimensional (semi-3D) flow-focusing microfluidic chip for droplet formation.

Semi-3-Dimensional 流聚焦微流控装置产生尺寸控制的聚乙二醇二丙烯酸酯液滴

Uniform and size-controllable poly (ethylene glycol) diacrylate (PEGDA) droplets could be produced via the flow focusing process in a microfluidic device. ...

工程学

A Microfluidic Platform to Study Bioclogging in Porous Media

Bacterial biofilms are found in several environmental and industrial porous media, including soils and filtration membranes. Biofilms grow under certain flow conditions and can clog pores, thereby redirecting the local fluid flow. The ability of biofilms to clog pores, the so-called bioclogging, can have a tremendous effect on the local permeability of the porous medium, creating a pressure buildup in the system, and impacting the mass flow through it. To understand the interplay between biofilm growth and fluid flow under different physical conditions (e.g., at different flow velocities and pore sizes), in the present study, a microfluidic platform is developed to visualize biofilm development using a microscope under externally-imposed, controlled physical conditions. The biofilm-induced pressure buildup in the porous medium can be measured simultaneously using pressure sensors and, later, correlated with the surface coverage of the biofilm. The presented platform provides a baseline for a systematic approach to investigate bioclogging caused by biofilms in porous media under flow conditions and can be adapted to studying environmental isolates or multispecies biofilms.

The present protocol describes a microfluidic platform to study biofilm development in quasi-2D porous media by combining high-resolution microscopy imaging with simultaneous pressure difference measurements. The platform quantifies the influence of pore size and fluid flow rates in porous media on bioclogging.

研究多孔介质中生物堵塞的微流体平台

Bacterial biofilms are found in several environmental and industrial porous media, including soils and filtration membranes. Biofilms grow under certain ...

环境科学

Patterning of Microorganisms and Microparticles through Sequential Capillarity-assisted Assembly

Controlled patterning of microorganisms into defined spatial arrangements offers unique possibilities for a broad range of biological applications, including studies of microbial physiology and interactions. At the simplest level, accurate spatial patterning of microorganisms would enable reliable, long-term imaging of large numbers of individual cells and transform the ability to quantitatively study distance-dependent microbe-microbe interactions. More uniquely, coupling accurate spatial patterning and full control over environmental conditions, as offered by microfluidic technology, would provide a powerful and versatile platform for single-cell studies in microbial ecology. 
This paper presents a microfluidic platform to produce versatile and user-defined patterns of microorganisms within a microfluidic channel, allowing complete optical access for long-term, high-throughput monitoring. This new microfluidic technology is based on capillarity-assisted particle assembly and exploits the capillary forces arising from the controlled motion of an evaporating suspension inside a microfluidic channel to deposit individual microsized objects in an array of traps microfabricated onto a polydimethylsiloxane (PDMS) substrate. Sequential depositions generate the desired spatial layout of single or multiple types of micro-sized objects, dictated solely by the geometry of the traps and the filling sequence. 
The platform has been calibrated using colloidal particles of different dimensions and materials: it has proven to be a powerful tool to generate diverse colloidal patterns and perform surface functionalization of trapped particles. Furthermore, the platform was tested on microbial cells, using Escherichia coli cells as a model bacterium. Thousands of individual cells were patterned on the surface, and their growth was monitored over time. In this platform, the coupling of single-cell deposition and microfluidic technology allows both geometric patterning of microorganisms and precise control of environmental conditions. It thus opens a window into the physiology of single microbes and the ecology of microbe-microbe interactions, as shown by preliminary experiments.

We present a technology that uses capillarity-assisted assembly in a microfluidic platform to pattern micro-sized objects suspended in a liquid, such as bacteria and colloids, into prescribed arrays on a polydimethylsiloxane substrate.

通过顺序毛细管辅助组装对微生物和微粒进行图案化

Controlled patterning of microorganisms into defined spatial arrangements offers unique possibilities for a broad range of biological applications, ...

Polydimethylsiloxane-polycarbonate Microfluidic Devices for Cell Migration Studies Under Perpendicular Chemical and Oxygen Gradients

This paper reports a microfluidic device made of polydimethylsiloxane (PDMS) with an embedded polycarbonate (PC) thin film to study cell migration under combinations of chemical and oxygen gradients. Both chemical and oxygen gradients can greatly affect cell migration in vivo; however, due to technical limitations, very little research has been performed to investigate their effects in vitro. The device developed in this research takes advantage of a series of serpentine-shaped channels to generate the desired chemical gradients and exploits a spatially confined chemical reaction method for oxygen gradient generation. The directions of the chemical and oxygen gradients are perpendicular to each other to enable straightforward migration result interpretation. In order to efficiently generate the oxygen gradients with minimal chemical consumption, the embedded PC thin film is utilized as a gas diffusion barrier. The developed microfluidic device can be actuated by syringe pumps and placed into a conventional cell incubator during cell migration experiments to allow for setup simplification and optimized cell culture conditions. In cell experiments, we used the device to study migrations of adenocarcinomic human alveolar basal epithelial cells, A549, under combinations of chemokine (stromal cell-derived factor, SDF-1&#945;) and oxygen gradients. The experimental results show that the device can stably generate perpendicular chemokine and oxygen gradients and is compatible with cells. The migration study results indicate that oxygen gradients may play an essential role in guiding cell migration, and cellular behavior under combinations of gradients cannot be predicted from those under single gradients. The device provides a powerful and practical tool for researchers to study interactions between chemical and oxygen gradients in cell culture, which can promote better cell migration studies in more in vivo-like microenvironments.

The control of chemical and oxygen gradients is essential for cell cultures. This paper reports a polydimethylsiloxane-polycarbonate (PDMS-PC) microfluidic device capable of reliably generating combinations of chemical and oxygen gradients for cell migration studies, which can be practically utilized in biological labs without sophisticated instrumentation.

细胞迁移研究在垂直化学和氧梯度聚二甲基硅氧烷的聚碳酸酯微流体装置

This paper reports a microfluidic device made of polydimethylsiloxane (PDMS) with an embedded polycarbonate (PC) thin film to study cell migration under ...

Microfluidic Platform with Multiplexed Electronic Detection for Spatial Tracking of Particles

Microfluidic processing of biological samples typically involves differential manipulations of suspended particles under various force fields in order to spatially fractionate the sample based on a biological property of interest. For the resultant spatial distribution to be used as the assay readout, microfluidic devices are often subjected to microscopic analysis requiring complex instrumentation with higher cost and reduced portability. To address this limitation, we have developed an integrated electronic sensing technology for multiplexed detection of particles at different locations on a microfluidic chip. Our technology, called Microfluidic CODES, combines Resistive Pulse Sensing with Code Division Multiple Access to compress 2D spatial information into a 1D electrical signal. In this paper, we present a practical demonstration of the Microfluidic CODES technology to detect and size cultured cancer cells distributed over multiple microfluidic channels. As validated by the high-speed microscopy, our technology can accurately analyze dense cell populations all electronically without the need for an external instrument. As such, the Microfluidic CODES can potentially enable low-cost integrated lab-on-a-chip devices that are well suited for the point-of-care testing of biological samples.

We demonstrate a microfluidic platform with an integrated surface electrode network that combines resistive pulse sensing (RPS) with code division multiple access (CDMA), to multiplex detection and sizing of particles in multiple microfluidic channels.

与复用电子检测的粒子的空间跟踪微流体平台

Microfluidic processing of biological samples typically involves differential manipulations of suspended particles under various force fields in order to ...

Reconfigurable Microfluidic Channel with Pin-discretized Sidewalls

Microfluidic components need to have various shapes to realize different key microfluidic functions such as mixing, separation, particle trapping, or reactions. A microfluidic channel that deforms even after fabrication while retaining the channel shape enables high spatiotemporal reconfigurability. This reconfigurability is required in such key microfluidic functions that are difficult to achieve in existing "reconfigurable" or "integrated" microfluidic systems. We describe a method for the fabrication of a microfluidic channel with a deformable sidewall consisting of a laterally aligned array of the ends of rectangular pins. Actuating the pins in their longitudinal directions changes the pins' end positions, and thus, the shape of discretized channel sidewalls.Pin gaps can cause unwanted leakage or adhesion to adjacent pins caused by meniscus forces. To close the pin gaps, we have introduced hydrocarbon-fluoropolymer suspension-based gap filler accompanied by an elastomeric barrier. This reconfigurable microfluidic device can generate strong temporal in-channel displacement flow, or can stop the flow in any region of the channel. This feature will facilitate, on demand, the handling of cells, viscous liquids, gas bubbles, and non-fluids, even if their existence or behavior is unknown at the time of fabrication.

A microfluidic channel with deformable sidewalls offers flow control, particle handling, channel dimension customization and other reconfigurations while in use. We describe a method for fabricating a microfluidic channel with sidewalls made of an array of pins that allows their shape to change.

基于 Pin 离散壁的可重构微流控通道

Microfluidic components need to have various shapes to realize different key microfluidic functions such as mixing, separation, particle trapping, or ...