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Fabrication of Refractive-index-matched Devices for Biomedical Microfluidics

机译:折射率匹配的生物医学微流控装置的制造

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摘要

The use of microfluidic devices has emerged as a defining tool for biomedical applications. When combined with modern microscopy techniques, these devices can be implemented as part of a robust platform capable of making simultaneous complementary measurements. The primary challenge created by the combination of these two techniques is the mismatch in refractive index between the materials traditionally used to make microfluidic devices and the aqueous solutions typically used in biomedicine. This mismatch can create optical artifacts near the channel or device edges. One solution is to reduce the refractive index of the material used to fabricate the device by using a fluorinated polymer such as MY133-V2000 whose refractive index is similar to that of water (n = 1.33). Here, the construction of a microfluidic device made out of MY133-V2000 using soft lithography techniques is demonstrated, using O2 plasma in conjunction with an acrylic holder to increase the adhesion between the MY133-V2000 fabricated device and the polydimethylsiloxane (PDMS) substrate. The device is then tested by incubating it filled with cell culture media for 24 h to demonstrate the ability of the device to maintain cell culture conditions during the course of a typical imaging experiment. Finally, quantitative phase microscopy (QPM) is used to measure the distribution of mass within the live adherent cells in the microchannel. This way, the increased precision, enabled by fabricating the device from a low index of refraction polymer such as MY133-V2000 in lieu of traditional soft lithography materials such as PDMS, is demonstrated. Overall, this approach for fabricating microfluidic devices can be readily integrated into existing soft lithography workflows in order to reduce optical artifacts and increase measurement precision.
机译:微流体装置的使用已经成为生物医学应用的定义工具。当与现代显微镜技术结合使用时,这些设备可以实现为能够同时进行互补测量的强大平台的一部分。这两种技术的结合所带来的主要挑战是传统上用于制造微流控设备的材料与通常用于生物医学的水溶液之间的折射率不匹配。这种失配会在通道或设备边缘附近产生光学伪影。一种解决方案是通过使用诸如MY133-V2000的氟化聚合物来降低用于制造器件的材料的折射率,所述氟化聚合物的折射率类似于水的折射率(n = 1.33)。在此,通过使用O2等离子体结合丙烯酸树脂支架来增加MY133-V2000制成的器件与聚二甲基硅氧烷(PDMS)基材之间的粘合力,展示了使用软光刻技术构造的由MY133-V2000制成的微流体器件的构造。然后通过将装有细胞培养基的设备孵育24小时来测试该设备,以证明该设备在典型成像实验过程中保持细胞培养条件的能力。最后,使用定量相显微镜(QPM)来测量微通道中活贴壁细胞内的质量分布。这样,证明了通过由低折射率聚合物(例如,MY133-V2000)代替传统的软光刻材料(例如,PDMS)来制造器件而实现的提高的精度。总体而言,这种制造微流体装置的方法可以很容易地集成到现有的软光刻工作流程中,以减少光学伪像并提高测量精度。

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