利用多晶矽奈米線場效電晶體無標記檢測肺癌miRNA生物標誌物

Abstract

早期肺癌的預後檢測，可以顯著提高病患的存活率。miRNA是一種短鏈的非編碼核糖核酸分子，存在於所有真核細胞中，並且在與人類腫瘤發生的相關基因當中。更是扮演非常關鍵的角色。而目前對於miRNA的檢測存在著不同挑戰和問題，像是費工耗時、低靈敏度、需標記等不同缺點。由於多晶矽奈米線場效電晶體 (pSNWFET)具有對高靈敏度、及時且免標記偵測的特性，而在發展一個功能強大的生物感測器上展現很好的潛力。本研究證實探針改質之多晶矽奈米線場效電晶體證實能夠專一且超靈敏的偵測肺癌相關的miRNA, let-7a 和 miR-21。對於在奈米線表面上專一的探針與目標物雜交之最適當的離子強度環境也有所驗證。除此之外，從肺癌細胞株萃取得到的miRNA萃取物被用來驗證多晶矽奈米線場效電晶體晶片可以在飛莫爾濃度下專一性的偵測到其中的miR-21-3p目標物。因此，在未來應用上多晶矽奈米線場效電晶體生物感測器將是一個能夠提供與肺癌相關之血液臨床樣品篩檢的平台原型。以多晶矽奈米線場效電晶體為基礎的之miRNA生物感測器應用在未來生物醫學和肺癌預後檢測可以是一項優良的選擇。

Prognosis of lung cancer at its early stages is vital for improving the survival rate of patients. MiRNAs are short non-coding ribonucleic acid molecules that play key roles in a class of genes involved in human tumorigenesis. Current methods for the detection of miRNA are facing different challenges and problems such as time-consuming, low-sensitivity and requirement for labeling. Polysilicon silicon nanowire field-effect transistor (pSNWFET) has great potential to be developed to a powerful biosensor because of its capability for highly sensitivity, real-time and label-free detection of nucleic acid. In this research, functionalized pSNWFET has been demonstrated to achieve specific and ultrasensitive detection of tumor-derived miRNAs, let-7a and miR-21, which may serve as biomarkers for lung cancer. Optimal conditions for specific target-probe hybridization on the nanowire surface were determined. Finally, miR-21 in A549 lung cancer cells extract was determined using pSNWFET and its sensitivity was found comparable to the standard qPCR method at femtomolar regime. We demonstrated in this study that a platform for the screening of miRNA associated with lung cancer in clinical serum sample can be achieved through a pSNWFET based miRNA biosensor. We expect that this platform can be an excellent choice for future application in biomedical and prognosis of lung cancer.