生物感測器及微混合器之三維數值模擬研究

Abstract

免疫檢測的工作原理主要是基於在生理環境中蛋白質配位體與受體間的專一性鍵結反應，此為在設計生物感測器上的一種自然特性。 本論文以有限元素軟體在三維的模型下分析一種常見的蛋白質（C-反應蛋白質）在生物感測器微流道中的結合反應動力學。一些會影響結合反應的因素都將在本文中討論，包括微流道的高度，微流道中是否有凹槽，入口處之流速，反應面的尺寸、排列及形狀。 在生物感測器的微流道中，由於垂直於反應面的流速很小，因此在微流道中的待測分子主要是藉由擴散作用傳輸到反應面上再與反應面上的探測分子結合。而在反應面上結合反應的速率通常快於待測分子藉由擴散作用傳輸到達反應面上的速率，因此整個反應過程被擴散傳輸所限制，為了增加反應的速率，本文提出了一種方法來提高生物感測器中免疫檢測的結合效率。藉由在微流道內施加非均勻的交流電場，由電熱效應產生的渦流可以對流場造成攪拌的效果，此流場的擾動可加速待測分子傳輸到反應面上的速率進而提高待測分子與探測分子結合與解離反應的效率。本論文設計了幾種擁有不同電極及反應面配置的生物感測器來探討電熱效應對結合反應的影響，經由不同配置的測試，我們可得到擁有較佳電極與反應面配置的生物感測器。在施加15伏特、100 的交流電下，C-反應蛋白質複合物的反應曲線的初始斜率可以在結合狀態提昇4.09倍，而在解離狀態可以提昇3.08倍。此外，藉由提高攜帶待測分子緩衝液的導電係數以及在微流道的壁上加入溫度控制，我們可以施加較低的電壓來加速結合反應的速率。基於模擬的結果，我們可改進生物感測器的設計，而這些數值數據對於設計生物感測器是非常有用的。 另外，在生物化學的應用上，常需要快速混合不同的流體樣本。在微奈米尺度下，流體的流動通常屬於層流，缺乏紊流使得擴散作用成為混合的主要機制。藉由在微流道內施加非均勻的交流電場，產生的電熱力將對微混合器中的流場造成擾動而因此提高了混合的效率。本論文以三維模型分析了以電熱效應增加混合品質的主動式微混合器，數值模擬結果顯示在微混合器的出口，兩種不同濃度的流體樣本，其混合品質將可提高至84％。

The working principle of immunoassays is based on the specific binding reaction of an analyte-ligand protein pair in physiological environments. It is a natural characteristic which is applied to design biosensors. In this work, we perform a three-dimensional (3-D) finite element simulation on the binding reaction kinetics of the common-used protein, C-reactive protein (CRP), in a reaction chamber (micro-channel) of a biosensor. Several crucial factors which influence the binding reaction in the simulation are discussed first, including the channel height, micro-channel with or without cavity, inlet flow velocity, and the dimensions, arrangement, and shape of the reaction surface. The flow velocity perpendicular to the reaction surface is so small that the analyte, which is supposed to bind to ligands on the reaction surface, is transported mainly by diffusion. The rate of the binding reaction on the reaction surface is usually large enough to restrain all analytes reaching there practically. Thus, the process is said to be diffusion-limited, and in order to increase the reaction rate, a technique is proposed to enhance the binding efficiency of immunoassay for a biosensor. By applying a non-uniform AC electric field to the flow in the micro-channel of the biosensor, the electrothermal force can be generated to induce a pair of vortices to stir the flow field. These swirling patterns in the fluid can accelerate the transport of the analyte to the reaction surface and hence enhance the association and dissociation of analyte-ligand complex. In this work, we design several types of biosensors with various arrangements of a pair of electrodes and the reaction surface to discuss the electrothermal effect on the binding reaction for a biosensor. For the arrangement of the biosensor we studied, the initial slope of the binding curve of the analyte-ligand complex versus time can be raised up to 4.09 times in association phase and 3.08 times in dissociation phase for CRP, respectively, under applying AC field of 15 peak-to-peak and operating frequency of 100 . Furthermore, by increasing the conductivity of the carrier solution and adding the thermal control on the walls of the micro-channel, we can accelerate the response of the binding reaction by applying a lower voltage. Based on these results, an improved design of the biosensor incorporating a pair of electrodes is demonstrated and the presented data of numerical simulation are useful in designing the biosensors. In addition, biochemical applications often require rapid mixing of different fluid samples. At the microscale level, the fluid flow is usually highly ordered laminar flow, and the lack of turbulence makes the diffusion be the primary mechanism for mixing. By applying a non-uniform AC electric field to the flow micro-channel, the electrothermal force can be generated to induce disturbance to the flow field and hence promote the mixing efficiency for the micromixer. A 3-D numerical investigation of an active micromixer, utilizing electrothermal effect to enhance its mixing efficiency, is proposed in this work. The numerical results show that a mixing quality of 84% can be achieved at the outlet of the micromixer.