以電子束微影技術製作之奈米電漿感測器整合自動化微流道控制系統進行生物分子檢測

Abstract

局域表面電漿共振（LSPR）是奈米金屬內透過電磁波作用使電子雲產生振盪的現象。由於具有即時，快速和免標籤檢測等優點，LSPR已應用於各種信號測量，例如生物感測。細胞激素是一組細胞之間溝通的信號分子，在免疫和炎症反應中有重要作用。而在感染期間，細胞激素的濃度會迅速增加。利用LSPR技術的各項優點，我們可以快速建構細胞激素的圖譜，達到即時的疾病診斷。首先，為了製造具有良好性能和效率的LSPR感測器，我們使用兩種奈米製程策略：快速熱退火（RTA）和電子束微影（EBL）。RTA感測器的靈敏度為196 nm / RIU，FOM為0.46，面積大(能夠達到公分等級)，而這種大面積的感測器能夠有更多的應用，像是多種抗原的檢測。另外，我們製造了具有優異性能的不同幾何形狀（正方形，三角形和圓形）的電子束感測器，靈敏度分別為270、219和230 nm / RIU，FOM分別為4.91、4.51和6.16。之後，我們將LSPR感測器與微流道，自動化微流控制系統和光學平台互相整合。最後，我們成功地應用於生物分子測量，像是IgG和我們目標的細胞激素TNF-α。因此，我們的LSPR傳感器和平台可以克服傳統技術的缺點，並在生物感測應用上能有顯著的貢獻。

Localized surface plasmon resonance (LSPR) is a phenomenon of oscillation of electron cloud irradiated by the light within noble metal nanoparticles. Due to the advantages such as real-time, rapid, and label-free detection, LSPR has been applied to various signals measurements such as biosensing. Cytokines, a group of cell-signaling molecules, play an important role in immunological and inflammatory responses. Moreover, during the infection, the concentration of cytokines can rapidly increase. Therefore, combining with the LSPR technique, we can rapidly construct the cytokine profiles. First, to fabricate an LSPR sensor with good performance and efficiency, we use two kinds of nanofabrication strategy; rapid thermal annealing (RTA) and electron beam lithography (EBL). The RTA sensor acquired a sensitivity 196 nm/RIU and FOM 0.46 and extremely large area with a cm scale. This large area sensor can have different applications such as multiple analyte measurements. Moreover, we fabricate different geometry (square, triangle, and circle) of the e-beam sensor with excellent performance, the sensitivity is 270, 219, and 230 nm/RIU, and FOM are 4.91, 4.51, and 6.16 respectively. Then, after acquiring an LSPR sensor, we combined the LSPR with microchannel, automatic microfluidics control system, and our optical platform. Finally, we successfully applied to biomolecule measurements such as IgG and our targeted cytokine TNF-α. We believe our LSPR sensor and platform have the potential to overcome the drawbacks of conventional techniques and show promising contributions in biosensing applications.