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研究生:吳家榮
研究生(外文):Chia-Jung Wu
論文名稱:應用鋯鈦酸鉛薄膜感測器觀察A549肺癌細胞受熱因子抑制之生長情況
論文名稱(外文):A study of using PZT membrane sensor to observe the growth of human lung cancer cell A549 inhibited by thermal effect
指導教授:吳嘉哲
口試委員:蔡肇基陳志敏蔡慶修許佳賢
口試日期:2011-07-13
學位類別:碩士
校院名稱:國立中興大學
系所名稱:機械工程學系所
學門:工程學門
學類:機械工程學類
論文種類:學術論文
論文出版年:2011
畢業學年度:99
語文別:中文
論文頁數:69
中文關鍵詞:PZT質量感測器A549肺癌細胞
外文關鍵詞:PZTmass sensorlung cancer A549
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本研究發展以圓型鋯鈦酸鉛薄膜式(PZT)之壓電材料製作出質量感測器。當微小質量貼附於感測器表面時,藉由共振頻率漂移的情況推算出貼附上之質量的大小。圓型薄膜式壓電感測器是由矽薄膜,PZT薄膜與一對電極所組成之,利用阻抗分析儀量測其訊號。在結構設計上,固定PZT薄膜之厚度為1μm與矽薄膜之半徑1000μm,以矽薄膜之厚度與電極面積作為設計參數。本研究利用有限元素軟體ANSYS計算感測器的性能。由模擬結果可知,矽薄膜之厚度會影響到感測器之初始頻率,再利用有限元素軟體設計結構之上電極的大小,電極之設計將影響到感測器的輸出,不可超過結構第一模態之反曲點。得最佳值約為結構半徑的60%。
接著將本裝置運用於生物感測上,本研究以A549肺腺癌細胞做為探討,以控制培養箱之環境溫度做為腫瘤細胞生長機制的抑制,當培養溫度高於正常培育溫度3~6℃時,腫瘤細胞會因而開始凋亡,以本研究之質量感測器量測細胞的變化量並以結構頻率飄移量作為依據,當培養相同的細胞濃度(cells/ml)於37℃與培養於43℃的情況下,結果發現培養於37℃的細胞變化,其頻率飄移約338Hz,而培養於43℃的細胞變化其頻率飄移約98Hz,可發現細胞在高於正常培養溫度3~6℃會有凋亡的現象產生,並成功的以本裝置量測出其變化。


In this study, we used a piezoelectric membrane actuated by a PZT thin film for mass-sensing applications. The form of the mass sensor was made circular, in order to increase signal performance with well to the square form. In this device, we can calculate the mass added on a sensing surface by the resonance frequency shift when micro-masses were coated on the sensing surface. This sensor consists of silicon thin film, PZT thin film and a couple electrodes, and measures the signal by impedance (4924A).
A finite element model is used to simulate the performance of sensor. By the result of simulation, the radius and thickness of silicon diaphragm will change the first resonant frequency of sensor. The thickness of PZT thin film and the size of top electrodes will affect the signal to noise ratio of sensor. In this thesis, 1μm PZT thin film and 80μm silicon diaphragm were used, because of the limitation of fabrication process. Radius of silicon diaphragm were chosen by 800μm and 1000μm to obtain first resonant frequency of sensor, 435 kHz and 275 kHz, respectively. The area of top electrode should be 60% of the area of silicon diaphragm to gain the maximum signal to noise ratio.
Piezoelectric sensors based on resonance frequency shift were then used to detect the mass at which the lung cancer cell A549 coats on the sensing surface. A549 cells were dip coated on the back side of silicon diaphragm, cultured in the incubator at 24 hours. After incubation, sensors were measured by impedance analyzer (Agielent 4294A) to get frequency shift and calculate the added mass on the silicon diaphragm. In this thesis, inhibition of A549 by temperature was also studied. A549 cells began apoptosis when culture temperature was higher than 37℃. The same concentration of A549 cells were incubated both at 37℃ and 43℃. After cultured for 24 hours at 37℃, A549 cells grew flourishing, and sensors detected frequency shift of 338 Hz. At 43℃, A549 cells almost perished, and sensors just observed frequency shift of 98 Hz.


致謝 I
ABSTRACT II
中文摘要 III
目錄 IV
圖目錄 VIII
表目錄 XI
第一章 序論 1
1.1研究動機與研究背景 1
1.2研究目的 2
1.3文獻之回顧 5
1.3.1目前已發展之生物感測器 5
1.3.2腫瘤細胞之抑制 13
1.4實驗上可能遭遇的困難點 16
第二章 相關理論 17
2.1壓電材料特性 17
2.1.1壓電效應 17
2.1.2介電效應 18
2.2壓電材料組成方程式 18
2.3阻抗分析 20
2.4熱傳遞分析 21
2.4.1穩態熱傳遞型態 21
第三章 微感測器設計與製作 24
3.1感測器之作動方式 24
3.2感測區域的尺寸設計 25
3.2.1感測反應區域外觀尺寸設計參數 25
3.2.2感測區域的模型建構之有限元素分析與模擬參數 27
3.3圓形薄板感測器之自由振動分析 29
3.4電極面積設計 33
3.5感測器製作流程步驟 36
3.6鋯鈦酸鉛(PZT)溶液製備配方 38
3.7 PZT薄膜製作流程 38
3.8薄板感測區矽之蝕刻 39
3.8.1 DRIE蝕刻選擇比 40
3.8.2 蝕刻深度 41
3.9 X-Ray繞射儀 41
3.10 PZT薄膜阻抗特性 42
第四章 細胞培養 43
4.1 A549肺癌細胞介紹 43
4.2細胞培養實驗設備與耗材器具 43
4.2.1設備 43
4.2.2耗材器具: 44
4.2.3實驗器材滅菌 44
4.2.4藥品 44
4.3細胞培養實驗步驟 45
4.4 細胞於試片培養之流程 46
第五章 微質量感測器之量測 48
5.1量測實驗儀器設備 48
5.2邊界條件固定之探討 48
5.3感測區域之形狀不同的差異 51
5.4 PZT極化 52
5.5結構之共振頻率量測 52
5.5.1阻抗分析儀4294A校正與量測步驟 53
5.5.2結構之共振頻率量測結果 54
5.4細胞受熱抑制分析與量測 57
5.4.1細胞在不同培養溫度下生長情況 57
5.4.2細胞在不同培養溫度下以PZT感測器量測凋亡情況 58
第六章 結論與未來展望 63
6.1 結論 63
6.2 未來展望 63
參考文獻 65


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