人工器官如心室輔助器、人工心瓣、氧合裝置等，會在心血管中造成非生理性的流況，這些流況所產生的血流應力會引發血液的破壞，特別是紅血球的損傷，稱為溶血。一般以溶血指數(Index of Hemolysis, IH(%))來表示，此溶血指數是切應力大小及暴露時間的函數。Giersiepen et al.(1990)依據Wurzinger et al.(1986)的實驗導出的溶血指數模式，IH(%) 。此模式廣被應用在計算流體力學(CFD)對新設計人工器官的評估上。新型人工器官經由此模式CFD所計算的溶血指數和實際原形的實驗值有相當大的差異。式中的應力是由簡單Couette黏度儀所產生之剪應力，而實際流場應包含有剪應力和拉伸應力。單由剪應力無法準確預估其溶血指數。因此本研究分別利用層流場與紊流場進行真實的紅血球破壞實驗，以了解其中的破壞機制。在層流實驗中，分別利用不同幾何形狀入口的短毛細管與微流道，其在進口端會產生一強烈的拉伸應力場，此流場先經由CFD的計算，求出其應力值，然後採用豬的新鮮紅血球，進行溶血的測試，以了解拉伸應力對溶血的影響。結果顯示和先前的研究結果是一致的，拉伸應力為紅血球破壞的主要機械力，且其閥值約為800-1000 Pa。在紊流實驗中，以軸對稱自由噴射流場所產生的紊流剪力場，進行溶血實驗。首先利用雷射都普勒流速儀(LDV)及質點影像流速儀(PIV)，進行流場的量測，再將清洗過的紅血球置入已知紊流應力的流場中，進行溶血實驗。先前的溶血被認為是紊流場中的雷諾應力所造成。近年來提出的假說認為和血球大小相當尺度的小渦流所形成的黏滯消散應力才是破壞血球的真正機械力。但由於受限於目前儀器的解析度，而無法量測到消散應力的最小渦流尺度，經由紊流場中可解析及次格點間的動力平衡假設下，由可解析所得的應變率張量中，利用Smagonrinsky的模式，則可估算紊流消散率，進而推求其黏滯消散應力。結果得到紅血球破壞的主軸切應力閥值為500 Pa，而黏滯消散應力為40 Pa，至少小於雷諾應力一個量級。此黏滯消散應力和層流的實驗結果比較也是除了差ㄧ個量級之外，其時間尺度小於三個量級。由此得知紅血球在紊流與層流中有不同的破壞機制，所以一個可靠的溶血指數模式必須完全了解紅血球在不同剪力場下的破壞機制。

Artificial prostheses such as left ventricular assist devices, artificial heart valves, and oxygenators can create non-physiologic flow conditions within the cardiovascular system. The stress forces generated in these flow fields can induce blood cell damage, particularly red blood cell damage or hemolysis. The Index of Hemolysis (IH; %) is affected by the magnitude of shear stress and exposure time. Giersiepen et al. (1990), based on experiments by Wurzinger et al. (1986), determined that the Index of Hemolysis can be calculated by IH(%) . This model has been widely used in computational fluid dynamics (CFD) for the evaluation of new artificial prosthesis designs. However, the IH calculated via CFD are often inconsistent with actual measured values from experiments done on prototypes. The stress value in the equation is based on the shear stress generated from a simple Couette viscometer; however, actual flow field forces include both shear stress and extensional stress. As such, the shear stress alone cannot accurately determine IH. We applied laminar and turbulent flow that was utilized to hemolysis porcine RBCs, in order to compare the IH derived. In laminar flow, we created a strong extensional stress flow field with the sharp contraction of short capillary and small channels. The flow field generated at the entrance of the capillary was calculated with CFD to determine the stress values, which was followed by hemolysis experiments with porcine red blood cells to determine the effects of extensional stress on hemolysis. Our results were consistent with prior studies in that the extensional stress was the primary mechanical force involved in hemolysis with a threshold value of 800-1000 Pa. In turbulent flow, We applied two-dimensional laser Doppler velocimetry (LDV) and particle image velocimetry (PIV) to measure the flow field of a free submerged axi-symmetric jet that was utilized to hemolysis the porcine red blood cells in selected locations. However, the resolution of current instrumentation is insufficient to measure the smallest eddy sizes. Assuming a dynamic equilibrium between the resolved and sub-grid scale (SGS) energy flux, the SGS energy flux was calculated from the strain rate tensor computed from the resolved velocity fields and the SGS stress was determined by the Smagorinsky model, from which the turbulence dissipation rate and then the viscous dissipative stresses were estimated. Our results showed that the hemolytic threshold of major principal Reynolds stresses is up to 500 Pa and the viscous dissipative stresses is 40-60 Pa, it’s at least an order of magnitude less than the Reynolds stresses. The viscous dissipative stresses for hemolysis also tend to be an order of magnitude lower than the laminar shear thresholds. In addition, the time scales are three orders of magnitude smaller than the laminar shear. Because of these differences, a reliable damage quantification model needs to fully understand about the varying mechanisms of blood cell damage by different shear stress conditions.

目錄	I
表目錄	III
圖目錄	IV
第一章 緒論	1
1.1 溶血與溶血模式	1
1.2 層流流場之研究	5
1.紅血球細胞的變形	5
2.拉伸應力	6
3.能量消散率	8
1.3 紊流流場之研究	10
1.噴射流	10
2. Kolmogorov尺度理論	10
3. 大尺度渦流模擬(Large eddy simulation)	12
4. 紊流溶血研究	13
1.4 研究目的與動機	16
1. 層流流場實驗	16
2. 紊流流場實驗	17
第二章 層流實驗方法與分析	18
2.1 短毛細管流場方法與分析	18
1. CFD流場模擬	18
2. 實驗設置	19
2.2 收縮微流道流場方法與分析	21
1. CFD流場模擬	21
2. 實驗設置	22
2.3 溶血實驗	23
第三章 紊流實驗方法與分析	25
3.1 質點影像流速儀量測與實驗設置	25
1. 流場設置	25
2. 質點影像流速儀系統	25
3. 大尺度渦流模擬(Large eddy simulation)分析	26
3.2 雷射都卜勒流速儀量測與實驗設置	31
1. 流場設置	31
2. 二分量雷射測速儀量測系統	31
3. 能量頻譜分析	32
第四章 結果與討論	37
4.1 短毛細管流場實驗結果	37
4.2 收縮微流道流場實驗結果	43
4.3 DPIV量測與溶血實驗結果	49
4.4 能量頻譜分析與溶血實驗結果	52
第五章 結論	55
5.1 層流中的溶血評估	55
5.2紊流中的溶血評估	56
5.3建議與未來展望	57
參考文獻	58








表目錄
表1-1-1 過去文獻中溶血閥值與暴露時間的關係表。	104
表4-1-1 短毛細管直角入口流場溶血實驗結果總表	105
表4-1-2 短毛細管斜角入口流場溶血實驗結果總表	106
表4-2-1微流道直角入口流場溶血實驗結果總表	107
表4-2-2 微流道斜角入口流場溶血實驗結果總表	108
表4-3-1噴射流場溶血實驗結果	109
表4-4-1 噴射流場溶血實驗結果(Ue=9.06 m/s)	110













圖目錄
圖1-3-1　噴射流能量的生成與消散曲線(Pope, 2000)。	70
圖1-3-2　紊流場中渦流大小之分布圖(Pope, 2000)。	70
圖2-1-1　流場模擬示意圖(a)軸向斷面(b)徑向斷面。	71
圖2-1-2　(a)孔口拉伸流場溶血實驗設置。1.活塞及血液儲存腔，2.伺服馬達，3.馬達控制器，4.短毛細管圓片，5.不銹鋼盤，6.血液樣品收集針筒。(b)直角與斜角短毛細管圓片尺寸圖。	71
圖2-1-3　流場實驗設置實體照。	71
圖2-2-1　微流道平板設計。(a)突縮狹縫微流道平板，(b)漸縮狹縫微流道平板	72
圖2-2-2　微流道模型設計。(1.微流道，2.微流道平板，3.壓克力，4.玻璃片，5.血液入口端，6.樣品收集端。)	72
圖2-2-3　微流道模型實體照。	73
圖2-2-4　流場實驗設置。(1.馬達控制器，2.伺服馬達，3.活塞，4.收集針筒，5.微流道模型。)	74
圖2-2-5　流場實驗設置實體照。	74
圖3-1-1　噴射流場溶血實驗設置圖	75
圖3-1-2　噴射流場溶血實驗設置實體照	75
圖3-2-1　實驗設置圖	76
圖3-2-2　亂流能量傳輸模式示意圖(Sheng, 2000)	76
圖4-1-1　直角進口流場各項應力分布圖及流線上的應力變化圖。(μ=17 cP，V=12 m/s) (a) τzz; (b) τrr; (c) τrz。流線函數(1) 3.71E-04 kg/s; (2) 2.54E-04 kg/s; (3) 1.39E-04 kg/s; (4) 6.07E-05 kg/s; (5) 0 kg/s。	77
圖4-1-2　斜角進口流場各項應力分布圖及流線上的應力變化圖。(μ=17 cP，V=12 m/s) (a) τzz; (b) τrr; (c) τrz。流線函數(1) 3.33E-04 kg/s; (2) 2.33E-04 kg/s; (3) 1.30E-04 kg/s; (4) 5.75E-05 kg/s; (5) 0 kg/s。	78
圖4-1-3　直角與斜角進口流場在不同黏滯度下各項應力與溶血指數IH之關係圖。(a)   ; (b)  ; (c)  。標準差為6次實驗的均方根值。	79
圖4-2-1　微流道流場在斷面Z=0.00025 m的各項應力分布圖(U=0.9 m/s，μ=17 cP)。(a)直角流場τxx；(b)直角流場τyy；(c)直角流場τzz；(d)斜角流場τxx；(e)斜角流場τyy；(f)斜角流場τzz。	80
圖4-2-2　微流道流場在斷面Z=0.00025 m的各項應力分布圖(U=0.9 m/s，μ=17 cP)。(a)直角流場τxy；(b)直角流場τyz；(c)直角流場τzx；(d)斜角流場τxy；(e)斜角流場τyz；(f)斜角流場τzx。	81
圖4-2-3　微流道流場在斷面Z=0.00025 m的各項應力分布圖(U=0.9 m/s，μ=17 cP)。(a)直角流場拉伸應力；(b)直角流場剪應力；(c)直角流場能量消散率；(d)斜角流場拉伸應力；(e)斜角流場剪應力；(f)斜角流場能量消散率。	82
圖4-2-4　用來計算個應立即寧量消散率之斷面位置標示圖。	83
圖4-2-5　不同入口流速下，各斷面的平均能量消散率的變化曲線圖。	83
圖4-2-6　在不同流場下之各項應力與溶血指數關係圖(a) ；(b)  ；(c)  。標準差為6次實驗的均方根值。	84
圖4-2-7　在不同流場下之各項應力與溶血指數關係圖(a)  ；(b)  ；(c)  。標準差為6次實驗的均方根值。	85
圖4-2-8　在不同流場下之各項應力與溶血指數關係圖(a)  ；(b)  ；(c)  ，標準差為6次實驗的均方根值。	86
圖4-3-1　噴射流場在不同出口流速下之平均軸向流速(m/s)等量線圖。(a)Ue=11.75 m/s；(b)Ue=9.70 m/s；(c) Ue=6.38 m/s。	87
圖4-3-2　噴射流場在不同出口流速下之雷諾應力(Pa)等量線圖。(a)Ue=11.75 m/s；(b)Ue=9.70 m/s；(c) Ue=6.38 m/s。	88
圖4-3-3　噴射流場在6.5D處斷面之平均軸向流速剖面曲線圖。	89
圖4-3-4　噴射流場在6.5D處斷面之雷諾應力剖面曲線圖。	90
圖4-3-5　噴射流場在6.5D處斷面之主軸應力剖面曲線圖。	91
圖4-3-6　噴射流場在6.5D處斷面之紊流黏滯切應力剖面曲線圖。	92
圖4-3-7　各項與溶血指數之關係圖。(a)雷諾應力；(b)主軸應力；(c)紊流黏滯切應力。	93
圖4-4-1　噴射流場的平均速度剖面圖(Ue =9.03m/s)	94
圖4-4-2　噴射流場的雷諾切應力RSS剖面圖(Ue =9.03m/s)	95
圖4-4-3　噴射流場的最大雷諾切應力RSSMaj剖面圖(Ue =9.03m/s)	96
圖4-4-4　噴射流場在X/D=4斷面上之能量頻譜函數圖(Ue =9.03m/s)	97
圖4-4-5　噴射流場在X/D=6斷面上之能量頻譜函數圖(Ue =9.03m/s)	98
圖4-4-6　噴射流場在X/D=8斷面上之能量頻譜函數圖(Ue =9.03m/s)	99
圖4-4-7　噴射流場的紊流黏滯切應力TVSS剖面圖(Ue =9.03m/s)	100
圖4-4-8　噴射流場的Kolmogorov尺度剖面圖(Ue =9.03m/s)	101
圖4-4-9　最大雷諾切應力RSSMaj與溶血指數Hp的關係圖。	102
圖4-4-10　紊流黏滯切應力TVSS與溶血指數Hp的關係圖。	103

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