循環腫瘤細胞濃縮結合電訊量測之晶片研製

癌細胞的轉移與擴散，是癌症患者常出現的死因，癌變過程中腫瘤細胞從原發腫瘤中分離，成為循環腫瘤細胞（CTCs）存在於循環系統中，而循環腫瘤細胞可做為早期癌細胞轉移徵兆之有效依據，亦可做為判斷病患預後之重要指標。但是在CTCs的偵測與鑑定上存在著一定程度的技術挑戰，因此即便CTCs具有重要的臨床診斷意義，循環腫瘤細胞的鑑定技術目前還是無法被廣泛的使用。本研究目的主要是在不破壞細胞之前提下且無需外加微幫浦及電源訊號產生器，製作手持式裝置針對血液中微量循環腫瘤細胞進行濃縮，利用圓形漸縮式電極擴大細胞濃縮區域，並以步進式電路施加電壓於相鄰兩電極，使細胞驅動於兩電極之強電場間，最後逐步聚縮於中央電極，達到細胞濃縮效果，並利用鎖相放大器對濃縮之細胞進行阻抗量測，對捕捉細胞後電極的電導與阻抗變化進行探討。實驗中顯示，當步進式電場切換時間為10s時，只需10Vpp電壓且頻率為1 MHz即可讓濃縮效率達到95%，利用鎖相放大器量測時，電極之電導與電容變化量則隨著細胞數量呈高度線性之增加，而阻抗則有隨細胞數量增加而逐漸減少之趨勢。

關鍵字

介電泳；循環腫瘤細胞；微流體；阻抗量測

並列摘要

Circulating tumor cells (CTCs) exist in the cancer patient's circulatory system, and they can be used as an effective basis for early signs of cancer metastasis, and an important indicator to determine the prognosis of patients. The present study develops a handheld electric module which provides stepping electric fields for dielectrophoresis (DEP) to concentrate the CTCs with low concentration about 500-1000 cells/mL. The transparent electrodes were fabricated by patterning the indium tin oxide (ITO) coated glass to observe the experimental results apparently. The volume of the open-top chamber on the chip for 100 μL processed the sample rapidly compared to conventional microchannels. Positive dielectrophoretic cells were guided toward the center of the microchamber due to the movement of the high-electric-field region. By using a lock in amplifier, the impedance was measure on the center of electrodes after concentrating the cells. The trend of changes in impedance on the electrode has been observed apparently. It was also confirmed that the proposed method realized the biosensor of CTCs detection.

並列關鍵字

dielectrophoresis ； impedance measurement ； circulating tumor cells ； microfluidic

參考文獻

[1]G. P. Gupta, J. Massagué, “Cancer Metastasis: Buliding a Framework,” Cell, 127: 679-695, 2011.

[2]Y.-K. Chung, J. Reboud, K.C. Lee, H.M. Lim, P.Y. Lim, Karen Y. Wang, K.C. Tang, H.M. Ji, Y. Chen, “An electrical biosensor for the detection of circulating tumor cells,” Biosensors and Bioelectronics, 26: 2520-2526, 2011.

[3]Cristofanilli M, G. T. Budd, M. J. Ellis, A. Stopeck, J. Matera, et al. “Circulating Tumor Cells, Disease Progression, and Survival in Metastatic Breast Cancer,” Seminars in oncology, 33: 9-14, 2006.

[4]J. S. de Bono, H. I. Scher, R. B. Montgomery, C. Parker, M. C. Miller, et al. “Circulating Tumor Cells Predict Survival Benefit from Treatment in Metastatic Castration-Resistant Prostate Cancer,” Cancer Therapy: Clinica, 14: 6302-6309, 2008.

[5]S. J. Cohen, C. J. A. Punt, N. Iannotti, B.H. Saidman, K.D. Sabbath, et al. “Relationship of Circulating Tumor Cells to Tumor Response, Progression-Free Survival, and Overall Survival in Patients With Metastatic Colorectal Cancer,” Journal of Clinical Oncology, 26: 3213-3221, 2008.

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循環腫瘤細胞濃縮結合電訊量測之晶片研製

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