| 研究生: |
劉正浤 Liu, Cheng-Hung |
|---|---|
| 論文名稱: |
以電旋轉晶片快速探討肺癌細胞對藥物與放射線敏感性影響 Study of Drug Susceptibility and Radiation Therapy Response for Lung Cancer Cells by Using Electrorotation Biochip |
| 指導教授: |
張憲彰
Chang, Hsien-Chang |
| 學位類別: |
碩士 Master |
| 系所名稱: |
工學院 - 生物醫學工程學系 Department of BioMedical Engineering |
| 論文出版年: | 2016 |
| 畢業學年度: | 104 |
| 語文別: | 英文 |
| 論文頁數: | 77 |
| 中文關鍵詞: | 電動力學 、電旋轉 、癌細胞 、藥物與放射線的反應 |
| 外文關鍵詞: | Electrokinetics, Cancer cells, Drug and the Radiation response test |
| 相關次數: | 點閱:214 下載:1 |
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現行標靶藥物如艾瑞莎與阿斯特捷利康,其主要治療對象為帶有上皮生長因子受體突變之癌症病患。由於肺癌目前高居癌症死亡率首位,若能於癌症早期即診斷出罹患肺腺癌則能有效增加預後效果並降低死亡率,如何在早期診斷並對症下藥即為目前最重要的課題。因此,一套快速檢測系統成為目前發展重點。此系統功能為快速檢測肺腺癌病患是否帶有上皮生長因子受體基因突變,以利醫生能對症下藥。而此系統亦能進一步應用於癌症腫瘤對於放射線治療反應檢測上,由於目前放射治療並無特殊生物標記能判定放射線對於病人是否有效,所以醫師只能根據從古至今所累積數據判斷後決定病患放射線劑量,而此系統則有望能給予醫生放射線劑量之依據。此檢測系統為一黃光微影製程生物晶片並輔以微流道製作,以利細胞微粒的傳送。此研究以兩種電動力學定理為發展核心:其一為介電泳力定理,功能為將分布於微流道內的癌細胞固定在電極之正中央。其二為電旋轉定理,功能為使固定於電極正中央之癌細胞旋轉,以利製做細胞的旋轉頻譜。利用細胞旋轉速度之差異,來快速判斷病患所帶有癌症基因是否為藥敏性,或放射治療敏感性。而實驗設計則有標靶藥物添加組與放射線治療組,藥物為艾瑞莎與阿斯特捷利康並將之靜置六小時等待藥性作用。放射線劑量為兩格雷至十格雷,並亦將細胞靜置七小時與三十一小時,藉由不同之劑量判斷癌細胞對於放射線的敏感性。細胞轉速改變之機制與細胞核內癌化訊息傳遞路徑的改變相關聯,標靶藥物治療方式為阻斷細胞核內訊息路徑的傳遞,放射線機制則為破壞細胞核內之DNA或活化p53基因等方式。本實驗利用此旋轉速度之變異可推測細胞電特性之改變,並可快速判斷藥物與放射線治療之效果,使醫師能以最短之判斷時間並給予病人最適當之治療方式。
The main Gefitinib and AZD9291 treatment groups are cancer patients with epidermal growth factor receptor (EGFR) mutations. Because of the high mortality rate in this cancer, early diagnosis is very important. Therefore, a rapid detection system is a developmental priority. This system can used to detect whether or not patients carry the EGFR mutation in order to compare the response of tumors treated by radiation therapy to those without treatment. Because there are no special biomarkers that can be used to decide whether or not radiation therapy is effective for cancer patients, doctors must decide dosages according to cumulative data. Therefore, it is hoped that the system proposed in this work will become the basis for doctors’ judgments. The proposed system is a type of biochip manufactured using photolithography. There are two theories applied in our research. One is dielectrophoresis (DEP) and the other is electrorotation (ROT). DEP is used to trap a cancer cell in a central electrode, and ROT allows the cancer cell to rotate stably. Then, using the differences in the rotational speed is possible to distinguish drug susceptibility and the response to radiation therapy in the case of cancer cells. There are target drug groups and radiation therapy groups in the experimental design. The target drugs are Gefitinib and AZD9291, which are incubated for a total of 6 hours. The radiation doses range from 2 Gy to 10 Gy. The rotational speed change is related to changes in the signaling pathways due to the influence of the target drug and the radiation. Therefore, using the difference of rotational speed to distinguish the effect of the drug and radiation is the focus of the experiment.
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