李百祺Li, Pai-Chi臺灣大學:電機工程學研究所程健銘Cheng, Chien-MingChien-MingCheng2010-07-012018-07-062010-07-012018-07-062008U0001-2907200801272200http://ntur.lib.ntu.edu.tw//handle/246246/187936本論文主要探討使用超音波聲速與光聲振幅變化量測葡萄糖濃度之可行性。對於糖尿病患而言，血糖量測是必要的檢測。目前最普遍的方法仍以侵入式的化學檢測法為主，而這會造成受測者傷口及痛苦。利用光聲效應最大的潛在優點為非侵入式及同時利用物質的光學特性以及聲學特性來判斷葡萄糖的濃度，本論文之研究目標即為探討此可行性。在光聲實驗架構方面，主要以Ti:sapphire作為雷射之光源，發出波長在940 nm的近紅外光照射葡萄糖溶液，並且用中心頻率為1 MHz，聚焦深度為1.27 cm之線聚焦超音波探頭以側向模式進行光聲波量測，並將所得訊號之振幅差異來分辨葡萄糖之濃度。為降低雷射輸出之變異所造成之影響，亦利用同步量測之雷射能量做修正。此結果顯示在光聲訊號的平均振幅方面，濃度每增加1%，平均振幅可上升2%，此與參考文獻數據相符合。光聲訊號振幅的標準差則大約是振幅的1.5%-2%，此誤差限制了實際應用之可行性。目前所知誤差來源包括系統內部所產生的熱雜訊，此經由訊號平均可有效降低；誤差來源也包括了雷射能量的變異，此則無法被完全去除。在聲速量測方面，使用中心頻率為20 MHz之探頭，在距離探頭下1公分處放置鐵板，量測脈衝回波。在距離為1公分之下，葡萄糖濃度每上升1%，飛行時間可下降約0.18%左右，而標準差大約是0.2 ns，其主要來自於jitter之影響。本研究目前結果仍以溶液實驗為主，此系統可分辨之濃度差為1%，而美國食品藥物管理局(FDA)則規定需能分辨濃度差為0.01%才可供人體使用，因此需要再降低標準差，並結合聲速參數去除受外界干擾之訊號。本研究也進行了血紅素溶液之初步實驗。在光聲訊號的平均振幅方面，葡萄糖濃度每上升1%，平均振幅會上升1.4%。在量測聲速方面，與純水溶液所得結果相似，聲速會隨葡萄糖濃度上升，而葡萄糖溶液濃度每上升1%，飛行時間下降約0.17%。In vivo的實驗將在未來進行，由於紅血球會造成光的散射，而且血漿中其他物質和葡萄糖吸收光譜重疊的問題，將不易產生良好的光聲訊號，因此可探討以多波長的方式來逐一消除其他物質的干擾及選擇適當量測部位來克服in vivo應用之相關問題。In this research, glucose concentration measurements based on photoacoustic(PA) signal amplitude and acoustic velocity are studied. Determination of blood glucose level is a required procedure in diabetes care. Currently, the most common method involves collecting blood samples for chemical analysis, but it is invasive and prone to result in pain and skin injury. It is the purpose of this study to investigate the feasibility of non-invasive glucose measurements based on PA and ultrasonic measurements. The PA setup includes a source Ti:sapphire laser and a line-focused single-crystal ultrasound transducer operating at 1 MHz. The transducer was arranged perpendicular to the incident laser beam for sideward detection. Our experiment results reveal that the PA amplitude increases by about 2% when the glucose concentration increases by 1%, and the standard deviation is around 1.5% to 2%. The standard deviation results from thermal noise, which can be decreased by signal averaging and the instable laser output. On the other hand, sound velocity was estimated by pulse echo measurements. The experimental setup included an ultrasound transducer operating at 20 MHz, with the distance between the ultrasound transducer and a reflector being 1 cm. The experiment results show that the time of flight decreases by 0.18% when the glucose concentration increases by 1% and the standard deviation is around 0.2ns, which is mainly caused by jitter. In conclusion, our measurements show that a 1% concentration change is detectable. However, the FDA requires a 0.01% detectability. We have also performed preliminary experiments with hemoglobin solution. Results show that the PA amplitude increases by about 1.4% and the time of flight decreases by about 0.18% when the glucose concentration increases by 1%. Future works will focus on improving the method by using multiple-laser wavelength, and to study influence of blood constituents.摘要..........................................................................................................Ⅰbstract................................................................................................. Ⅲ錄..........................................................................................................Ⅴ目錄......................................................................................................Ⅶ目錄......................................................................................................Ⅹ一章　緒論............................................................................................1.1　研究動機....................................................................................1.1.1　糖尿病..............................................................................1.1.2　糖尿病判定......................................................................2.2　侵入式血糖量測........................................................................4.3　非侵入式血糖量測....................................................................4 1.3.1　GlucoWatch......................................................................4 1.3.2　光學量測..........................................................................5.3.3　螢光量測..........................................................................7.3.4　旋光量測..........................................................................8.3.5　阻抗量測..........................................................................9.3.6　非侵入式量測總結........................................................10.4　光聲效應簡介..........................................................................12 1.4.1 光聲效應........................................................................12 1.4.2　光聲效應目前之相關研究領域....................................13 1.4.3　光聲效應接收方式........................................................14.5　研究目標..................................................................................17.6　論文架構..................................................................................18二章　葡萄糖溶液光聲特性..............................................................19.1　葡萄糖溶液近紅外光吸收特性..............................................19.2　葡萄糖溶液熱學及聲學特性..................................................21.3　近紅外光波長產生之光聲訊號..............................................22.4　水溶液與組織液、血液之差異..............................................23三章　誤差理論基礎..........................................................................263.1　誤差傳播..................................................................................26.1.1　系統及隨機誤差............................................................26.1.2　誤差傳遞播定律............................................................273.2　The Cramer-Rao Lower Bound................................................29四章 實驗架構..................................................................................314.1　光聲振幅..................................................................................314.2　聲速..........................................................................................35五章　結果與分析..............................................................................385.1　光聲振幅-濃度變化.................................................................38 5.1.1　水溶液............................................................................38 5.1.2　硫酸銅溶液....................................................................425.2　聲速-濃度變化.........................................................................46六章　討論與結論..............................................................................486.1　雷射系統..................................................................................486.2　葡萄糖溶液..............................................................................516.3　訊號接收系統..........................................................................51.4　純水與硫酸銅之比較..............................................................536.5　溫度的影響..............................................................................556.6　聲速..........................................................................................576.7　結論..........................................................................................596.8　未來工作..................................................................................60 6.8.1　多波長雷射二極體發射系統........................................60 6.8.2　組織液、全血及in vivo實驗.........................................62獻回顧..................................................................................................691848826 bytesapplication/pdfen-US光聲效應非侵入式量測葡萄糖濃度振幅聲速photoacousticnoninvasiveglucose concentrationamplitudesound velocity[SDGs]SDG3thesishttp://ntur.lib.ntu.edu.tw/bitstream/246246/187936/1/ntu-97-R95921043-1.pdf