應用可量產之微流體篩選晶片分離人類血液中的轉移性癌細胞

Abstract

循環癌細胞 (circulating tumor cells, CTCs) 檢測是一可期待且對病人較少傷害癌症轉移檢測方法。臨床中癌症造成的死亡有九成是來自於癌細胞的轉移，其轉移路徑通常經由進入血管後轉移至腦、骨髓、肺臟、肝臟或其他器官。然而目前循環癌細胞檢測仍未被常規性使用於疾病管理，其中一個原因來自於稀少細胞的汲取困難。本工作及透過一內含以尺寸為篩選標準的微過濾結構之微流晶片從血液中汲取循環癌細胞，其製造方法為精密塑膠射出成形的壓克力製微結構熱壓接合到以電腦數值控制铣床製的壓克力儲存槽。廣範圍之癌症細胞株 (K562, MCF7, PC3 與 Colo205) 被微結構抓取後以螢光染色並以螢光顯微技術計數。結果顯示此晶片之穩定與易用性，以上述細胞株加入一毫升血液 (稀釋為十五毫升) 模擬病人檢體中的循環癌細胞抓取，其回收率達到七至八成。故此微流晶片應擁有讓循環癌細胞檢測成為更可用之癌症管理工具之潛力。

The detection of circulating tumor cells (CTCs) is a promising harmless in vitro diagnosis of metastasis. Cancer metastasis leads to roughly 90% of deaths of cancer patients. However, CTC detection has not been routinely used for disease management, where one reason for this is the difficulty associated with enrichment of these extremely rare cells. This work presents a microdevice to enrich CTCs from peripheral blood by a size-limiting microfilter structure. This PMMA structure is microinjection-mold and bonded onto a CNC-milled reservoir. Cells from a wide range of cancer cell lines (K562, MCF7, PC3 and Colo205) are captured on the structure, immunohistochemically stained and enumerated with fluorescent microscopy. Results show the chip is robust and ease to use. The recovery yield of cells spiked into 1mL of whole blood (diluted to 15mL) attained 70% to 80%. This microdevice should have potential to enable CTC-detection a more viable in cancer management.