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標題: | 血液之兆赫波光譜學 Investigation on THz Spectra of Ex vivo and In vivo Blood |
作者: | Tzu-Fang Tseng 曾子芳 |
指導教授: | 孫啟光(Chi-Kuang Sun) |
關鍵字: | 兆赫波,血液,頻譜技術,近場影像, THz,blood,spectroscopy,near-field imaging, |
出版年 : | 2015 |
學位: | 博士 |
摘要: | 血液在自然界中是最複雜的混合液體之一,用以輸送許多油脂、葡萄糖、鹽類、與蛋白質等分子至身體各處。這些生化分子的多寡與行為和許多疾病比如凝血不全症及高血脂症等有關。然而目前檢驗這些分子沒有非體外的方式,而體外檢驗中最常使用的生化與光學方法需要先做血漿血球分離,才能進行血液成分分析。兆赫波在近二十年的研究中已被指出對許多生化分子的震動和轉動非常靈敏,相較於現行的檢驗方法,兆赫波是唯一有機會觀察活體內全血中的分子運動並做檢測的工具。
為了發展兆赫波在血液檢測上的應用,我們首先欲找到在血液中對兆赫波敏感的分子。由於血液中眾多成分在不同個體中有濃度差異,最客觀與快速的找尋方式為適量採樣並做統計分析。在本論文中我們先取29位未加抗凝劑,與29位加了抗凝劑(肝素)的體外血檢體(符合取樣前空腹八小時的標準),做即時性及長時間的兆赫波頻譜量測,並將其測得的折射率與吸收常數與血液檢驗項目做相關分析。我們發現在頻率低於一兆赫的波段,血液吸收常數與血小板數目呈正相關,而此現象應是由血小板引發的凝血初階段的血小板凝集與凝血酶原活化反應造成。然而後階段的血液固化過程在統計上並未看出其對血液吸收常數造成上升或下降的作用。而在沒有凝血反應的血液中我們發現,三酸甘油脂在正常範圍內,和高頻的兆赫波血液的兆赫波吸收呈現負相關;而對所有的血液樣本,其低頻的兆赫波吸收由紅血球數目主導,並與紅血球數目有負相關。 為了未來非侵入式醫療檢測的應用,我們架設了一個近場穿透式兆赫波影像系統來量測在頻率低於一兆赫的波段,活體內的血液折射率與吸收常數。我們利用本實驗室過去提出的低損耗與低發散角度的管型兆赫波波導當平行光發射源,方便在其發射端固定活體動物,並以開口為次波長大小的金屬方形波導當能量接收器,在活體樣本表面近場距離內做二維掃描,以分辨出組織中次波長直徑的血管。實驗結果在活體裸鼠耳朵中,兆赫波穿透影像能成功顯現血管的所在位置。根據過去實驗與文獻得到的組織折射率,吸收常數,與血液折射率的值,與已知的吸收常數上限,我們利用數值模擬輔助與實驗結果比對,得到組織與活體內血液吸收常數差異很大(大於等於80cm-1),而根據血液吸收常數的上限(不大於水的吸收常數)與組織的吸收下限(不小於油脂的吸收常數),血液與組織的折射率最高能相差到0.3左右。另外,我們也進一步利用數值模擬,量化血液吸收常數變化造成血管能量穿透率的變化,以方便未來非侵入式檢測之應用。 以上的結果對未來兆赫波在血液檢測的研究上有實質的幫助。 Blood is the most complicated body fluid in the world which sends many kinds of biomolecules such as cholesterol, triglyceride, glucose, and proteins to organs and tissues. These molecules are related to many diseases such as coagulating problem and hyperlipidemia, that can only be examined ex vivo in nowadays. For the most common used biochemical and optical examination methods, blood centrifuge is needed to separate blood cells and plasma. In the past two decades THz has been indicated to be sensitive to the vibrational and rotational motions of many kinds of biomolecules. Comparing to the existing examination methods, THz waves is one of the candidates to noninvasively observe the molecular behaviors in whole blood. To develop futuristic applications in blood examination in THz region, we first need to find out the molecules of which the motions dominantly affect the THz spectrum of the whole blood. Since the concentrations of many biomolecules differ among individuals, it is necessary to collect a number of blood samples and have statistical analysis to efficiently find out these dominant molecules. In this thesis we have collected 58 ex vivo whole blood samples following 8-hours fasting guideline, 29 without adding anticoagulant and another 29 with heparin added, to have immediate and time-dependent THz spectra acquisition and analyze the correlation between the refractive indices and absorption coefficients to the examined hematological and biochemical factors. We have observed that the THz absorption coefficient of the whole blood without anticoagulant had a positive correlation to platelet count. This positive correlation is attributed to the platelet induced biochemical reactions including platelet deformation, platelet aggregation, and protein activations, in the beginning of blood coagulation. However, during the clotting process that change blood from the fluidic to the solid phase, no significant correlation between THz absorptions and time was found, indicating that THz is not sensitive to this phase transition. On the other hand, in the whole blood samples with heparin added to block the coagulation process, we have found that their absorption coefficients in the low sub-THz frequency region were dominated by the red blood cell count with a negative correlation. At high sub-THz frequency region, their absorption coefficients were dominated by the concentration of triglyceride with also a negative correlation. For futuristic non-invasive application, we have built a sub-THz in vivo near-field system for vessel imaging, adopting waveguided illumination and near–field scanning detection with a subwavelength aperture, to investigate the in vivo blood absorption coefficient and refractive index. Nearby blood vessels could be clearly resolved in our THz images, with a lateral resolution of around 0.5mm. The near-field pattern of the power transmittance through the vessel has also been numerical simulated and was found to have good correspondence to the measured results. According to the refractive indices of the tissue and the blood obtained in previous researches, as well as the well-known upper limit of the absorption coefficient of blood and the lower limit of the absorption coefficient of living tissue, our study indicated a small refractive index difference (at most 0.3) and a large absorption coefficient difference (at least 80 cm-1) between blood and surrounding tissues. The relationship between the power transmittance variation and the absorption coefficient variation of blood was also quantified with the help of numerical simulation. These works help in developing futuristic blood examination applications in THz region. |
URI: | http://tdr.lib.ntu.edu.tw/jspui/handle/123456789/54018 |
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顯示於系所單位: | 光電工程學研究所 |
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