微流體晶片與軟性感測晶片之整合製程及剪應力梯度晶片的開發

Abstract

本研究開發剪應力梯度產生器(shear stress gradient generators, SSGG)，與提出SSGG與濃度梯度產生器(Concentration gradient generator, CGG)及軟性感測晶片之整合技術。CGG是使用單步稀釋的微流道網路設計，並能夠在寬廣的輸入流量範圍內表現出高通量之特性。合成CGG的方法是利用電路與微流道網路之間的類比計算出混合流道的等效流阻，透過每個混合流道之間的流阻差異，能夠控制樣本液與緩衝液流入各個混合流道的體積混和比，並進一步在微流道出口產生預定義之濃度分布，透過此方法成功生成了線性(Linear)之濃度梯度。設計的SSGG原理是根據使用者定義之剪應力比例而計算出相對應的流道長度。濃度梯度產生器整合元件和剪應力梯度產生器整合元件皆透過微影製程(Photolithography)技術將其製成三層的微流道結構，並將三層PDMS層與軟性感測器整合。CGGs是透過將樣本液與緩衝液通入元件中進行量測，量測結果與理論值的誤差在5%之內，且在1.8至18 µL/min的流量範圍內能夠維持穩定的濃度梯度分布。SSGGs是透過量測液體在出口毛細管中的流速以計算出剪應力，線性和二次對數(2-fold logarithmic)之SSGGs的量測結果與理論值的誤差皆在5%之內，且在13 µL/min的流量範圍內能夠維持穩定。

This work presents the integration of gradient concentration generators (CGGs), shear stress gradient generators (SSGGs), and fluidic sensing devices. The CGGs, which can be synthesized by using a proposed algorithm, exhibits high throughput with a wide range of input flowrates. The proposed CGG-synthesizing algorithm calculates the equivalent channel flow resistances, which control the volumetric mixing ratios of the CGG mixing channels to generate predefined concentration gradient profiles. The optimization of the flow resistance ratios for realizing smallest footprint of microfluidic chips was performed in this work. In addition, microfluidic networks for generating various shear stress gradients were also designed and implemented. The SSGGs regulate fluid shear stress by varying the channel lengths to obtain appropriate flow velocity of each channel. The CGGs and the SSGGs are fabricated and implemented using the standard soft lithography technique. The microfluidic chip consists of three layers made from PDMS. A polymer-based glucose sensor is also integrated with each chip during the PDMS bonding process. The concentration gradient profiles of CGGs were measured by dye visualization. The error between the analytical profile and measured concentration profile is less than 5%. The generated concentration profiles were independent of the flow rate within the range of 1.8 to 18 µL/min. The performance of SSGGs is determined by measuring the marching velocity of a capillary meniscus for each microchannel. The shear stress on the sidewall of a channel can be evaluated by the associated velocity. The measured results show that the proposed SSGGs produce precise shear stress gradients for the designs of the linear and logarithmic profile (R2 is higher than 0.997 for both cases). In addition, the discrepancy between the measurement results and analytical profiles is approximately 1%–5%.