氮化物表面增益拉曼散射:核酸檢測及生物藥製備的新式微陣列晶片

This project is to develop a microarray biochip that can be applied in nucleic-aciddetection and the process control of biopharmaceutical manufacturing.Specifically, a pioneering microarray will be fabricated on the epitaxial wafercontaining nitride quantum wells (QWs), with which a large active area of strongsurface-enhanced Raman scattering (SERS) effect is used as a unique tool todetect the binding events of target molecules. SERS is a label-free technique that can detect numerous biomolecularinteractions in a single spectrum. If the SERS detection is performed with amicroarray format, hundereds (even thousands) of target molecules can besimultaneously analyzed on a tiny chip. Such high-throughput capability isparticularly attractive for the application in biopharmaceutical (or biologic)manufacturing, which is in desperate need of the process analytical technologyfor real-time and multiplex characterization of the processed materials. However,SERS-based microarray is extremely difficulty to be realized. The challenge liesin two obstacles: i) the very limited SERS-active area (< 10 nm); ii) the veryunstable signal intensities. The 1st obstacle is due to the fact that SERS signalsare usually confined within the tiny “hot spot”, i.e. the nanoscale plasmonicjunction with boosted Raman signals. With the hot spot smaller than a typicalprobed region (the circular region with the diameter above 2 μm) in themicroarray, most of the probed regions would deliver blank signals. The 2ndobstacle is caused by the thermal diffusion of the target molecule under laserexcitation, which results in severe intensity fluctuation as the heated moleculediffuses in and out of the tiny hot spot. These issues make it impossible to reliablytrack the analytes with SERS. In this project, we address the issue by nanostructured InGaN QWs, which isyet explored in the realm of SERS detection. The QW wafer is grown by metalorganic chemical vapor deposition (MOCVD), an ideal tool for industrial massproduction. We demonstrate that the InGaN QWs greatly enlarge the SERSactive region through a wafer-scale charge coupling mechanism, expanding the表CM02 計畫主持人：賴昆佑 申請條碼編號：110WFA0710171共 2 頁第 1 頁highly localized hot spot into the hot “surface”. The unique hot surface, spreadingover tens of microns, not only allows the microarray fabrication, but also rendersmuch stabilized SERS signals. Further, we also aim to build a high-speed SERSmapping system via the beam-expansion technique, which is expected to reducethe time for data acquisition and analysis. The new technology, combiningsemiconductor epitaxy and microarray biochip fabrication, is proposed tosubstantially advance the development of high-sensitivity, high-throughput andreal-time biosensors.