以深紫外光微影技術製造之次微米蛋白質微圖形應用於細胞生物學之研究

Abstract

在基礎的細胞生物學研究中，細胞必須被培養在特定的位置或形成某種順序以構成有組織的結構。而蛋白質微圖形是目前於微米級尺寸中，最被細胞生物學所廣泛運用的結構。然而，在某些特定的研究中，實驗結果與距離或圖形尺寸的精準卻有著極大的關聯性，因此，在更進一步的研究中，次微米蛋白質微圖形的製造是確實必要的。 在本篇論文中，我們成功的製造出次微米蛋白質微圖形，為了製造次微米蛋白質微圖形，某些新的步驟被導入深紫外光微影之微接觸印刷法，如TEOS膜、RIE 蝕刻與AR3塗層。為了彈性的深寬比需求，我們採用硬幕技術，於光阻層與矽基材間加入TEOS膜，此技術可增加其蝕刻選擇比。根據實驗的結果，藉由蝕刻參數的控制，深寬比可被控制於1.5至4.5之間。當圖形尺寸進入次微米時，矽基材與PDMS層間之黏著問題會更為嚴重，此外亦與微圖形之尺寸、間距與形狀有強烈的關係。因此，我們分析其間之化學機制並選擇適當的材料做為緩衝層來避免矽基材與PDMS層間產生鍵結，我們選用了AR3層為緩衝層並成功減輕了矽基材與PDMS層間之黏著問題。最後，我們觀察神經與細胞生長於此特殊設計之次微米蛋白質微圖形的情況。這些新研發的製程可成功導入深紫外光微影之微接觸印刷法，並可藉此製造出有組織的表面結構，可利於細胞生物學之廣泛應用。

In fundamental cell biology studies, cultured cells need to be positioned at specific location and in certain orders to create organized structures. Protein patterns are the most widely used as the structures in cell biology with micro size. In some specific investigations, the experimental results are strong dependence with the accuracy of distance or pattern size. Thus, protein micropatterns with accuracy of sub-micro are indeed required for further research. In this thesis, we successfully demonstrated the realization of fabricating protein sub-micro patterns for cell biology applications. To successfully generate the protein sub-micro patterns, some new designed procedures were involved into the DUV photolithography with micro contact printing process, such as TEOS film, RIE etching and AR3 coating. For the requirements of flexible aspect ratio , TEOS film was added as a hard mask between photoresist and substrate for increasing the etching selectivity. According to our experimental results, the aspect ratio could be offered from 1.5 to 4.5 by RIE recipe tuning. When the pattern size is into sub-micro level, the sticking issue between silicon and PDMS will be getting worse. Besides, it also has very strong dependence with pattern sizes, pitches and shapes. We analyze the chemical mechanisms and select suitable material to be the buffer layer to avoid the crosslinking from these two materials. The AR3 layer was employed to be a buffer layer and successfully reduce the issue of pattern sticking in sub-micro size. After that, we observed the neuron and cell outgrowth in these special designed protein sub-micro patterns. The investigated patterning process that combining with DUV photolithography and micro contact printing could be used to generate functional surfaces for cell biology applications