選擇性成長奈米感測材料對於螢光生醫感測與矽奈米元件氫偵測之影響

Abstract

本論文聚焦在選擇性沉積奈米材料並應用於感測器。第一個部分，整合氧化鋅奈米結構感測元件與微流道重力血球分離技術合成一個單一系統來進行全血的生物分子偵測。首先利用COMSOL模擬氧化鋅奈米結構表面反應速率與實際全血分離實驗設計出分離效果最佳的微流道結構，選出最好的奈米結構以及最有效的腔體設計將血球過濾，以降低螢光訊號的干擾並提高抗體抗原結合的數目。接著運用生物相容性佳的氧化鋅奈米柱結構，增加感測表面積，提升螢光感測之動態範圍(Dynamic Range)與靈敏度(Sensitivity)。修飾感測抗體是利用單層自組裝技術(self-assembly monolayer)完成；在玻璃基材成長氧化鋅奈米線後，依序修飾3-氨基丙基三甲氧基矽烷(3-aminopropyltrimethoxysilane, APTMS)與雙琥珀醯亞胺辛二酸酯 (disuccinimidyl suberate, DSS)，以及前列腺特異性抗體8A6 (PSA antibody 8A6)。全血檢體則添加不同濃度已接合螢光抗體的前列腺特異性抗原，利用螢光分析元件可偵測到100 ng/mL至1 ng/mL的抗原濃度，氧化鋅奈米柱結構的使用更可以鑑別出5 ng/mL與1 ng/mL的差別。再利用流道修飾的方式，可以同時偵測不同的檢體。本研究將成為簡易型居家醫療檢測儀器的原型:採用少量的40 μL檢體，同時達到分離血球與低濃度抗原鑑別的便利性，及時提供疾病罹患的判讀，對可攜式生醫晶片的普及有重大的幫助。 論文第二個部分研究主要利用焦耳熱效應選擇性沉積白金(Platinum)於元件上做為氫氣感測器使用，並成功利用焦耳熱效應行self-heating在室溫下做即時的不同濃度氫氣量測。首先利用離子佈值技術控制矽奈米元件摻雜濃度，(n+/n-/n+)的元件結構設計可精準的控制元件放熱區域(低摻雜濃度區域)，並利用低濃度摻雜區域對閘極電位變化靈敏的特點作為感測區使用，先利用COMSOL多重物理偶合模擬不同電壓下表面溫度分布，與後續選擇性燒除PMMA以及不同電壓自加熱相互驗證。由原子力顯微鏡量測證實感測區表面之PMMA被完整燒除，進而進行選擇性沉積不同大小及厚度的金屬層。在處於不同濃度氫氣環境下的電性量測上，先在真空中找出對於偵測氫氣最佳的金屬層條件，並比較在不同操作電壓下對氫氣的反應時間變化，定出最佳的量測條件使得在真空中可靈敏的偵測50 ppm氫氣。另外發現在高溫且長時間的操作下元件的感測特性可得到顯著提升。最後在大氣環境的量測上，將元件置於利用PDMS製作出的小腔體內可使元件在大氣下擁有跟在真空狀態下一樣靈敏的吸附及脫附特性，最低偵測濃度可到達2.5 ppm。並且我們利用焦耳熱的方式，利用原子層化學氣象沉積系統(ALD)來在特定區域沉積白金，並且拿來當作氫偵測器。我們相信此充分利用焦耳熱效應技術作為氫氣感測器的應用可提升元件在室溫下的應用以及判斷不同濃度的氫氣準確性，以及可以選擇性的沉積不同的物質，來偵測不同的氣體，我們可以預期此技術對於後續相關的氫氣感測有重大的幫助。

This dissertation emphasizes selective deposition of nanomaterials for sensing applications. In part I, a biosensing platform integrating a blood cell separation microfluidic device and a zinc oxide nanowire fluorescencesensing structure were investigated and demonstrated for prostate specific antigen (PSA) detection. Blood cells usually cause signal interference during detection and decrease the efficiency of the antigen/antibody reaction in the whole blood assay. Therefore, an effective microfluidic channel chamber for blood cells separation was designed via the help of COMSOL simulation. An optimal microfluidic channel chamber dimension of 25 mm in width, 8 mm in height and 200 μm in thickness can attain a blood cell separation rate of 98.9%. A sharp ZnO nanowire (NW) with a cone-like structure increases the surface area and its improved fluidity enhances the capture efficiency of target molecules. Therefore, sharp ZnO NWs were grown in the microfluidic channels to enhance the dynamic range and the sensitivity of detection. Prior to sensing, 3-aminopropyltrimethoxysilane (APTMS), disuccinimidyl suberate (DSS) and PSA antibody 8A6 were modified on the ZnO nanowires via the self-assembly process. Whole blood samples spiked with various concentrations of PSA plus fluorescent PSA antibody 5A6 were characterized to evaluate the proposed system. This platform also presents the capability to distinguish PSA concentration in blood at 10 ng/mL, 5 ng/mL and 1 ng/mL. Based on this configuration, we successfully demonstrate that the detection of more than one target molecules can be fulfilled simultaneously on the same microfluidic device. With a very simple structure and needing only 40 μL sample, this prototype platform provides promising results as a future portable lab-on-a-chip. In part II, we report the experimental results of selective deposition of platinum on nanodevices as real-time hydrogen sensors by localized Joule heating. The active channels of nanobelt devices consisted of a n+/n-/n+ structure, and localized Joule heating was induced at the local high resistance region. The surface temperature was estimated by COMSOL simulations at different biases. Atomic force microscope (AFM) was used to investigate the removal of poly (methyl methacrylate) PMMA, and monitor the different lengths and thicknesses of platinum deposition. First, responses of different hydrogen concentrations in vacuum were characterized. The results show that the coverage of catalyst material on the sensing region are proportional to sensitivity, while catalyst thickness is inversely proportional to sensitivity. Furthermore, different self-heating voltages were applied to accelerate the response and recovery time, and increase the detection limit to 50 ppm. A small detection chamber further improve the detection limit under atmosphere is about 2.5 ppm. In addition, devices after high voltage and long-time stress exhibited an improvement in sensing. This modification functioned well and exhibited nearly the same sensitivity as when in vacuum, as demonstrated with the equilibrium dissociation rate constant calculation. Moreover, the Pt can be successfully grown on the sensing region of the polysilicon nanobelt devices (PNDs) by atomic layer deposition, with current responding significantly during H2 detection.