光學光譜與顯微術於生物醫學之應用

Application of Optical Spectroscopy and Microscopy in Biomedicine

郭倫彰(Lun-Zhang Guo)

指導教授 ： 黃義侑

國立臺灣大學/工學院/醫學工程學研究所/博士(2022年)

https://doi.org/10.6342/NTU202200584

摘要

現代醫療技術有兩個主要趨勢：一是微小化，在細胞分子層級釐清病生理關聯，達成早期診斷與精準治療；二是非侵入式，期望在無創、低介入的前提下，協助疾病的診斷與追蹤。然而，這兩項趨勢在臨床上卻相互衝突，微分子檢測一般不能在活體內進行，而非侵入式檢驗則無法提供細胞分子層級的資訊。
生醫光電是將光學技術應用於生物醫學檢測、診斷或治療的新興熱門領域。生物體常見的輔酶NADH、FAD，具有特異性的螢光光譜，可用以監測細胞組織的代謝活性且不需添加染劑或顯影劑。加上非線性光學技術提供檢測深度，卻仍可維持次微米及的解析度。光學檢測技術的低介入、特異性、高靈敏度、高解析度等特點，使其具有非常大的潛力開發活體代謝檢測工具。
本論文主要是應用光電技術到生物醫學領域，包含三個應用研究：脂肪細胞代謝研究，急性腸繫膜缺血(AMI)研究，及腫瘤光動力療法研究。
脂肪細胞代謝研究是與臨床醫師合作，採集病患脂肪組織進行NADH與FAD的雙光子螢光檢測，分析螢光與糖尿病的關聯性。前期成果顯示糖尿病患的脂肪組織FAD與NADH的螢光均較對照組弱。
急性腸繫膜缺血研究是以大鼠模型進行血液螢光檢測，分析AMI大鼠血液螢光的變化。結果顯示AMI會造成血液螢光顯著上升，最早能在缺血50分鐘時看出變化。血液螢光有機會做為一個AMI早期篩檢的指標。
腫瘤光動力療法研究是利用非線性光學技術開發可以提升其作用深度的新型載體。我們利用特殊結構的金奈米花生產生表面電漿共振，以接收NIR雙光子激發，再將能量轉供給光敏劑釋出單線氧，產生細胞毒性殺死腫瘤細胞。並在組織細胞與動物活體中驗證其安全性與有效性。

關鍵字

自體螢光分子 ； 非線性光學 ； 脂肪組織 ； 急性腸繫膜缺血 ； 光動力療法 ； 奈米花生

並列摘要

There are two trends in modern medical technology: one is miniaturization, which clarifies the pathophysiological relationship at the cellular and molecular level to achieve early diagnosis and precise treatment; the other is non-invasive, which is expected to diagnose and track with low intervention. However, these two trends are in conflict in the clinic, with micromolecular assays generally not being performed in vivo, and non-invasive assays failing to provide information at the cellular and molecular level.
Biomedical optoelectronics is an emerging hot field that applies optical technology to biomedical detection, diagnosis or treatment. Common coenzymes NADH and FAD in organisms have specific fluorescence spectra, which can be used to monitor the metabolic activity of cells and tissues without adding dyes or imaging agents. In addition, nonlinear optical technology provides detection depth, but still maintains sub-micron and sub-micron resolution. The characteristics of low intervention, specificity, high sensitivity, and high resolution of optical detection technology make it have great potential to develop in vivo metabolic detection tools.
This dissertation mainly applies optoelectronic technology to the field of biomedicine, including three studies: the study of adipocyte metabolism, the study of acute mesenteric ischemia (AMI), and the study of tumor photodynamic therapy.
The study of adipocyte metabolism is to cooperate with clinicians to collect patient adipose tissue for two-photon fluorescence detection of NADH and FAD, and analyze the correlation between fluorescence and diabetes. Preliminary results showed that the fluorescence of FAD and NADH in the adipose tissue of diabetic patients was weaker than that of the control group.
In the study of acute mesenteric ischemia, blood fluorescence was detected in a rat model, and the changes of blood fluorescence in AMI rats were analyzed. The results showed that AMI caused a significant increase in blood fluorescence, with changes visible as early as 50 minutes of ischemia. Blood fluorescence has the opportunity to be used as an indicator for early screening of AMI.
Tumor photodynamic therapy research is the use of nonlinear optical technology to develop a new type of carrier that can enhance its depth of action. We use the special structure of gold nanopeanut to generate surface plasmon resonance to receive NIR two-photon excitation, and then transfer the energy to the photosensitizer to release singlet oxygen, which produces cytotoxicity to kill tumor cells. And verify its safety and effectiveness in tissue cells and animals.

並列關鍵字

auto-fluorescent molecules ； nonlinear optics ； adipose tissue ； mesenteric ischemia (AMI) ； photodynamic therapy (PDT) ； nanopeanut

參考文獻

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