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I. Fabrication of microfluidic channel systems and components in poly(dimethylsiloxane). II. Analysis of reactions of proteins using charge ladders and capillary electrophoresis.

机译:I.在聚(二甲基硅氧烷)中的微流体通道系统和组件的制造。二。使用电荷阶梯和毛细管电泳分析蛋白质的反应。

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Microfluidic devices find application in the fields of medicine, defense, and research, because they are often less expensive and more efficient than traditional devices, and potentially disposable. The marriage of microfluidic devices with organic polymers has accelerated their advancement because of the ease and speed with which they can be prototyped. The first section of this thesis describes two aspects of the development of microfluidic systems in poly(dimethylsiloxane)—general methods of fabrication and functional components for specialized applications.; Chapter 1 provides an overview of recent progress in three-dimensional channel systems and Chapter 2 presents in detail one of the first, general methods for fabricating such systems-the “membrane sandwich” method. This technique consists of overlaying different levels of features to build up a network of microfluidic channels with any connectivity. It enables the assembly and sealing of a stack of membranes to an arbitrary height and without tedious alignment steps.; As a step closer to fully integrated devices with multiple functions, and towards the original inspiration of the “lab-on-a-chip”, components for microfluidic systems are being developed to diverse ends. Valves, pumps, mixers, and sensors control the way fluid flows in microfluidic channels. Chapter 3 presents the fabrication of some of these components and demonstrates their capabilities. In particular, the biomimetic “lymphatic” valve that functions similarly to its biological counterpart (from which its structure was adapted) highlights the parallels between microfluidic systems and living systems—which, is shown here to be useful as an engineering tool.; The second part of this thesis addresses an important question in physical-organic chemistry and drug design: to what extent can residues on a protein communicate with other residues or ligands by electrostatic forces in aqueous solution? The present study combines organic syntheses, capillary electrophoresis, and mathematical modeling of kinetics. Its results are consistent with theory that invokes electrostatic potential alone as the stimulus for a change in the association behavior of residues as far away as 30 Å at ionic strength of 130 mM.
机译:微流体设备在医学,国防和研究领域得到了应用,因为它们通常比传统设备便宜,效率更高,并且可能是一次性的。微流体装置与有机聚合物的结合加速了其发展,因为它们的原型制作容易且速度快。本文的第一部分描述了聚二甲基硅氧烷中微流体系统开发的两个方面,即通用的制造方法和专用的功能部件。第1章概述了三维通道系统的最新进展,第2章详细介绍了制造此类系统的第一种通用方法,即“膜三明治”方法。该技术包括覆盖不同级别的功能,以建立具有 any 连接性的微流体通道网络。它可以将膜堆组装和密封到任意高度,而无需繁琐的对准步骤。为了向具有多种功能的完全集成的设备迈进,并朝着“片上实验室”的原始灵感迈进,微流体系统的组件正在发展到各种各样的目的。阀门,泵,混合器和传感器控制着流体在微流体通道中的流动方式。第3章介绍了其中一些组件的制造方法,并演示了它们的功能。尤其是,仿生的“淋巴”瓣膜的功能类似于其生物学对应物(从中改编了其结构),突显了微流体系统和生物系统之间的相似之处,在这里被证明可以用作工程工具。本论文的第二部分解决了物理有机化学和药物设计中的一个重要问题:蛋白质上的残基在水溶液中可以通过静电力在多大程度上与其他残基或配体连通?本研究结合了有机合成,毛细管电泳和动力学的数学模型。其结果与理论相吻合,该理论仅将静电势作为刺激,以改变离子强度为130 mM的残基的缔合行为,该残基最远可达30。

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