基因晶片製程 及 無光罩曝光系統模擬設計之研究

Abstract

基因晶片在分析去氧核糖核酸(Deoxyribonucleic Acid ; DNA)序列時，是一有效的工具。而「高密度」的基因晶片，更能在短時間內快速且有效地分析大量的DNA序列。本實驗的目的是在一片大小為七厘米乘以六厘米(7mm×6mm)的矽晶片上，製作出一萬個(一百乘以一百)微反應方格陣列，並在每一個面積為五十微米乘以五十微米(50μm×50μm)的微反應方格中，分別植入不同的標準DNA序列。以這種高密度的基因晶片並利用基因雜交比對的方式來篩檢DNA序列，只需要少量的檢體，在短短幾十分鐘內，就可以檢驗上萬種的DNA序列。 本論文的方向有二： 一、研究基因晶片的微影製程；二、模擬設計一無光罩式的曝光系統。由於微影製程方法需要製作並使用大量的光罩，與繁瑣的曝光步驟，全程約兩個月，非常耗時。為了改進上述的缺點，我們嘗試模擬設計出一套有高對比的成像品質的無光罩式光學曝光系統，其中以「數位微鏡片陣列元件(Digital Micromirror Device； DMD)」來替代光罩，將來可利用電腦控制，快速的得到與光罩曝光效果相同的曝光圖案。如此，再配合另一種不同的光化學合成方法，將可快速地在幾天之內，製作出高密度的基因晶片。

High-density oligonucleotide probes arrays are the powerful new tools for large-scale DNA and RNA screening, rapid detection of mutations in gene, expression monitoring, and gene discovery and mapping. By utilizing photolithography technique in this experiment, our goal is to synthesize a 100×100 oligonucleotide microarray on a 7mm×6mm silicon chip. Each unit for a single kind of oligonucleotide to grow onto is of 50μm×50μm wide. In this work, we found a protocol of photolithography for synthesizing our high-density 19-mer-oligonucleotide microarray. However, this method requires 76 photolithographic masks and takes two months to finish a single gene chip, which is expensive and time consuming. Therefore, we studied a different method, a maskless array synthesizer to replace the chrome masks with virtual masks generated on a computer by the use of a digital micromirror device (DMD). We have simulated a maskless-exposure-system (MES), which forms an image of the pattern on the DMD on the silicon chip. We also obtained a satisfactory modulation transfer function (MTF) of the simulated MES. With this maskless approach, relatively inexpensive gene chip can be synthesized in days.