奈米粒子散射與表面電漿共振影像偵測系統晶片

Abstract

本文以發展可攜式及高通量生物分子感測平台為目標，分別針對其感測理論、電路設計、及分析演算法作初步的探討。在相關的電路測試及偵測實驗中，已成功的利用CMOS影像感測器(CIS)、可程式化邏輯閘(FPGA)仿真模擬電路板與顯示電路，量測到半徑不同之奈米金粒子所發出之散射光訊號，對本實驗室所研發之偵測系統架構做了初步的驗證。 利用奈米粒子作為標記的生物分子可做為生物晶片的影像掃瞄反應樣本，經由偵測生物晶片表面奈米粒子散射光線的強度，可以分辨出相關基因或蛋白質晶片探針與標的物之雜交結合效率。奈米粒子有多種的偵測方式在近來的研究中被提出，在微小與晶片化上有具體的成果，並證實其可行性與正確性。在此將針對其中光偵測的方式做討論，奈米粒子散射光偵測系統之優勢為高通量並且與之前所廣泛使用的螢光分子檢測方式較為類似；不同於以雙波段雷射光激發螢光分子，再利用光電倍增管接收訊號的方式，奈米粒子標記的感測原理是經由漸逝波激發表面電漿共振，能夠以透射、反射與散射方式觀察到由金屬奈米粒子所發出的光訊號 [6]。 目前在實驗中所發展出的影像擷取系統，使用CMOS影像感測器模組做為光感測元件，接收奈米粒子所散射出來的光訊號，將光線強度轉換成數位信號之後，傳輸到可程式邏輯閘，以便於進行計算與顯示的處理。為便於分析影像感測器應用於生物晶片應用上的特性，另外一組實驗設計則是利用市售的網路攝影機，規格為解析度30萬畫素的CMOS影像感測器，利用USB傳輸到個人電腦，並使用軟體做分析。實驗成果目前已經能夠經由光線強度與色彩比值針對不同的奈米金粒子大小做辨別。

The goal of this study is to develop a high throughput and portable biomolecules detecting system. Discussions of the detecting theory, circuit design, and the analysis algorithm are disclosed respectively. In related circuit tests and detecting experiments, the measurement of the scattering optical signals which emitted from various sizes of gold nanoparticles through CMOS image sensor (CIS), field programmable gate array (FPGA) emulation board, and video display circuit system had successfully achieved. Thus there is the preliminary verification for this detection system structure. Biomolecules labeled with nanoparticles are able to be used as the reacted samples for biochip image scanning. By detecting the light intensity of nanoparticles scattering on the surface of biochip, it can distinguish the hybridization efficiency of target and probe regarding to relative gene or protein. Several detection methods have been provided in recent studies, to minimize and to integrate system on a single chip already has been implemented and the feasibility and validity have been proven. This study focuses on the light detection approach. The nanoparticles scattering light detection has the advantage of high throughput and is compatible with conventional fluorescence dye labeling method; however the detection is not excited by laser beam and received by photo multiplier tube. The optical signal comes from the evanescent wave induced surface plasmon resonance and observing is allowed by means of transmission, reflection and scattering [6]. The system utilized to capture image includes a CIS module as the light receiving device. After catching the light signal generated by nanoparticles scattering, CIS transfers the light intensity to digital signals and transmits to FPGA to do the processing of calculation and display. Another experimental setup uses a commercial web camera to analyze the characteristics of image sensor in biochip application. The specification of web camera is 300K pixel resolution and this camera connects to personal computer by USB interface. The image analysis is done by software and already can identify the differences between various size nanoparticles through light intensity and color ratio.