自從成功開發了標靶藥物，除了效果較好，相對於傳統治療的副作用也較低，為癌症病人帶來更多的希望。但隨之卻發現標靶藥物對不同人其療效各異。例如，肺癌細胞的表皮生長因子受體突變與非小細胞肺癌對標靶藥物敏感性有關，具有表皮生長因子受體突變的病人對表皮生長因子受體標靶藥物的反應顯著高於未具有突變的病人。因此為了正確的治療，病患都會接受表皮生長因子受體突變分析。然而傳統的檢測方法如基因定序、聚合脢連鎖反應檢測、化學免疫組織檢測，都相當耗時且也較為昂貴。故我們將以介電泳技術結合微流體晶片並輔以影像分析系統發展出快速的藥敏性檢測平台。本研究架構主要分為兩個部分：(1)優化三維電旋轉生醫晶片。在傳統的電旋轉晶片上仍有許多待解決的問題，當電旋轉訊號的頻率太高時，會讓細胞受到正介電泳力的吸引往電極移動，使電旋轉圖譜在高頻沒辦法分析，亦或細胞在旋轉時會有旋轉軸不固定的現象，導致在量化分析轉速時出現有極大的誤差，造成數據不具可信度。經過訊號的調控與電極結構的優化，我們發展出新一代的三維電旋轉生醫晶片，在最佳條件的電控制下，已能讓細胞在電極中間穩定旋轉的比例從20%上升到80%，有效的解決傳統電旋轉晶片旋轉不穩定等問題。(2)利用介電泳法進行肺癌細胞的藥物敏感性試驗。此研究將三維電旋轉晶片是否能應用於肺癌細胞對上皮生長因子標靶藥物反應的快速判定。實驗結果發現當標靶藥物對癌細胞有反應，在特徵頻率時的轉速會有明顯變慢的趨勢；而對標靶藥物沒有反應的癌細胞，在特徵頻率時的轉速則無明顯的改變。故此方法能夠利用轉速的變化來辨識癌細胞的對藥反應與否，且整個檢測流程耗時不超過兩小時，能夠大幅縮短檢測時間。

Molecular-targeted therapeutics for cancer bring hope to patients, providing higher efficacy and lower toxicity than conventional treatment. However, the benefit of the target drug in the treatment of lung cancer will be limited, unless the patients would be screen properly. For instance, the lung cancer patients with Epidermal Growth Factor Receptor (EGFR)-activating gene mutations have a better prognostic and longer medium survival time than the patients without mutations under EGFR tyrosine kinase inhibitor (TKI) treatments. Thus, EGFR mutation test is now the standard protocol for EGFR TKI treatment in lung cancer patient. The traditional EGFR mutation tests such as DNA sequencing, PCR, and IHC are relatively expensive and time-consuming. Here, we try to improve drug susceptibility test by using the on-chip electrokinetics assay combining with image analyzing system to create a novel detecting platform. In this thesis, two subjects will be discussed, (1) Optimization of the 3D ROT biochip There are many problems in the traditional ROT technology. For example, the cell could not be rotated in the center of electrodes when the frequency of ROT signal increased and the axis of rotation was not fixed. These reasons caused the unreliable ROT spectrum. Therefore, we developed a novel ROT technique to solve these problems. After optimizing the parameters, the cell could be rotated stably in the whole frequency range. (2) Dielectrophoresis-based drug susceptibility test In the second part, the application of ROT on rapid diagnosis of EGFR TKI susceptibility in lung cancer was tested. In the susceptible lung cancer cell lines, significant changes in ROT behavior can be observed. In contrast, the resistant cell lines, there was no significant changes in ROT behavior. In summary, the techniques of electrokinetics, microfluidics and the image analyzing system were integrated into this novel platform for rapidly detecting cancer cell drug sensitivity.

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