菲涅耳數位全像顯微系統於全血細胞分析之研製;Research and Development of Fresnel Digital Holographic Microscope System for Complete Blood Cell Analysis

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题名:	菲涅耳數位全像顯微系統於全血細胞分析之研製;Research and Development of Fresnel Digital Holographic Microscope System for Complete Blood Cell Analysis
作者:	陳臆鈞;Chen, Yi-Chun
贡献者:	生物醫學工程研究所
关键词:	光學成像;菲涅耳;全像術;傅立葉轉換;全血細胞;optical imaging;Fresnel;holography;Fourier transform;complete blood cell
日期:	2020-08-20
上传时间:	2020-09-02 15:30:04 (UTC+8)
出版者:	國立中央大學
摘要:	光學顯微鏡在工程物理、生物醫學等領域中扮演著相當重要的角色，藉由它觀察肉眼無法看到的表面材料、細胞或是微生物，但目前光學成像平台的複雜性和昂貴的成本使其在實際應用上有所限制。本研究中使用菲涅耳數位全像術(Fresnel Digital Holography, FDH)原理研發建立了新式數位全像顯微系統，利用純量繞射理論簡化了光學成像設備，不再需要龐大且複雜的光學元件，只需由非同調光、針孔和影像傳感器組成，沒有了透鏡限制視場(Field of view, FOV)大小，可同時具備廣視場(30mm2)並達到接近繞射極限之高空間解析度，透過控制光源的空間相干性在傳感器上記錄繞射影像，在不需光學透鏡下藉由傅立葉轉換重建出與20倍顯微鏡相同解析度之影像，經由自主研發之演算程式，僅需5秒內即可取得最終影像重建結果。在本篇論文中以全血細胞分析進行實際應用，在搭配自主設計的微流道採血晶片後，紅血球與白血細胞計數的準確率分別可達到93.5%與91%。本研發之系統在生物學和醫學診斷創新性的突破，有機會增加疾病的提前預防和早期診斷的可能性，尤其在醫療資源有限的環境。實驗結果證實本系統只需微量血液即可進行快速、大面積的血液細胞表徵分析與全血計數功能，可預期為現有的全血分析工具提供便攜且具有經濟效益的替代方案。 ;The optical microscope, which enabled people to observe invisible objectives more details such as surface materials, cells, or microorganisms played an important role in various fields of engineering, physical science, medicine, and biology. However, the application was limited by the complexity and expensive cost of the current optical imaging platform. The Fresnel Digital Holography (FDH) proposed in this study utilized scalar diffraction theory to simplify optical imaging equipment. It no longer needed large and complicated optical components were composed of non-coherent light, pinhole, and image sensor. Without the lens to limit the field of view (FOV), the high spatial resolution close to the diffraction limit could be achieved on a large FOV (30mm2). By controlling the spatial coherence of the light source, the diffraction pattern was recorded on the sensor, and the image with the same resolution as the 20x microscope was reconstructed by the inverse Fourier transform without any optical lens within 5 seconds. The accuracy of red blood cell count is 93.5%, and that of white blood cell is about 91%. The system will not only bring the innovative breakthroughs in biology and medical diagnosis, but also enhance the possibility of early prevention and early diagnosis, especially in areas where the medical resources are scarce. In this study, the complete blood cell analysis was used for practical application. After matching with the micro-channel blood sampling chip by self-designed, the empirical evidence obtained from in the experimental results proved that the system could perform rapid, high-throughput blood cell characterization analysis and the function of complete blood count with the trace blood sample. The system provided a portable and economical alternative of the contemporary whole blood analysis tools.
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