為了在奈米尺度上精確量測細胞內部結構，本研究結合高數值孔徑光學成像系統與部分波光譜學 (PWS) 技術，並利用有限差分時域法 (FDTD) 模擬其光散射及成像結果，以期提高傳統光學顯微鏡的解析極限，特別適用於早期癌症診斷等生物醫學應用。
傳統光學顯微鏡因解析極限限制，難以分辨小於200奈米的細胞結構，這對於早期疾病診斷造成挑戰。本研究提出一種數值模擬方法，旨在克服此限制。透過FDTD精確模擬細胞內部複雜奈米結構之間的散射過程。FDTD作為一種全波數值方法，透過FDTD能完整捕捉不同形狀與介質分佈所產生的全角度散射光，包括那些包含豐富高空間頻率資訊的大角度散射成分，為後續成像提供可靠的電磁場數據。
高NA系統能有效收集來自奈米結構的大角度散射光，這些光線承載著關於細胞精細結構的豐富高空間頻率資訊，是增加繞射解析度並提升圖像解析度的關鍵。FDTD模擬獲得的散射場數據經由近遠場轉換後，再結合向量繞射理論與Debye-Wolf積分等方法，模擬經高NA透鏡收集與再聚焦後的成像過程，重建出高解析度的細胞結構圖像。
透過此模擬框架，我們得以量化光散射光譜特性，並探討細胞內奈米尺度結構的折射率變化如何影響成像結果。結合部分波光譜學 (PWS) 分析，利用一維光學干涉頻譜對亞波長尺度折射率變化有高度靈敏性，能夠檢測細胞內奈米尺度結構的折射率變化，從而區分正常細胞與癌細胞的微小差異。
本研究驗證了高數值孔徑光學系統結合FDTD模擬在提升細胞奈米結構診斷能力上的潛力，期望為區分正常細胞與癌細胞提供新的數值工具，進而為早期癌症檢測等生物醫學應用提供創新視野。

This study combines high numerical aperture (high-NA) optical imaging with partial wave spectroscopy (PWS), utilizing the Finite-Difference Time-Domain (FDTD) method to simulate light scattering and imaging. Typical optical imaging systems involve four fundamental stages: illumination, scattering from the sample, collection of scattered light, and refocusing for image formation. Our aim is to overcome the diffraction limit of conventional microscopy for subwavelength cellular structures, particularly for early cancer diagnosis.
Conventional microscopy struggles to resolve cellular structures below 200 nm due to the diffraction limit. To address this, we employ Gaussian-profiled plane waves as the incident source. FDTD accurately simulates their scattering from complex nanoscale cellular structures by directly solving Maxwell's equations in space and time, comprehensively capturing full-angle scattered light, including high spatial frequency components crucial for imaging.
To enhance resolution, we simulate the collection capabilities of a high-NA optical system. Unlike low-NA systems that often neglect large-angle scattered light, high-NA lenses efficiently collect these information-rich rays, which carry high spatial frequencies essential for resolving fine details and are vital for breaking the diffraction limit. FDTD scattering data, after Near-to-Far Field Transformation, are then combined with vector diffraction theory and the Debye-Wolf integral to model high-NA collection and refocusing, reconstructing high-resolution cellular images.
This framework quantifies light scattering spectral characteristics and explores how refractive index variations in nanostructures affect imaging. Integrating PWS analysis, this study validates the potential of high-NA imaging combined with FDTD simulation in enhancing diagnostic capabilities for cellular structures, and we expect to provide a new numerical tool for early cancer detection and other biomedical applications.

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