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研究生: 邱彥超
Chiou, Yan-Chao
論文名稱: 高準確度之可攜式血液凝固檢測儀之設計及其臨床驗證
Design and Clinical Verification of High Accurate Portable Blood Coagulation Instrument
指導教授: 楊慶隆
Yang, C.-L.
學位類別: 碩士
Master
系所名稱: 電機資訊學院 - 電機工程學系
Department of Electrical Engineering
論文出版年: 2012
畢業學年度: 100
語文別: 中文
論文頁數: 137
中文關鍵詞: 凝血酶原時間光學檢測電阻抗分析重點照護檢驗
外文關鍵詞: Prothrombin time, Optical sensor, Impedance analysis, Point-of-care testing
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  • 本論文提出一個光學與電阻抗式可攜式血液凝固檢測儀,可準確地量測微量全血之凝固時間;並且結合無線傳輸應用於遠距離照護及監測,使病患可隨時隨地進行凝血時間的檢測。目前醫用及市面上的偵測凝血儀器價格昂貴,不適合個人購買及居家使用,因此我們提出並實作完成一套使用光學檢測,可直接偵測全血的儀器。
    本儀器使用透射光法可藉訊號一階微分之最大加速點準確判斷出凝血時間。光檢測系統使用德州儀器生產之單晶片(MSP430F149)進行控制、類比數位轉換、與數位信號處理,並經由光檢測元件、類比濾波、數位濾波以優化檢測結果。另一方面,我們同時採用另一個常見之檢測方法進行比較,電阻抗分析法使用阻抗分析儀由一階微分判斷凝血時間。
    為了驗證系統的可重複性,進行40次實驗,變異係數(Coefficient of Variation, CV)為2.29%,證實系統檢測結果重複性高。臨床實驗使用167管全血,每管重複兩次於攝氏37度之溫室進行實驗,實驗結果取第一次結果進行統計,由臨床實驗結果可驗證本自製儀器具有高度之準確度,與大型儀器(ACL TOP)比較相關係數(R)達0.956,並已經過167組實驗驗證,證明系統穩定性。藉由本論文研究得知凝血訊號受RBC、Fib、Hct的影響,並可由凝血訊號與CBC數據進行統計分析,結果顯示第一次實驗及第二次實驗的最大加速點斜率與Fib有高度相關性。本論文所提出之凝血檢測儀具有可攜式、高準確度、成本低廉、使用簡單、直接偵測全血、並使用藍芽無線傳輸等優點,可達成遠距離照護以及降低社會醫療成本的優勢。

    This thesis presents a portable blood coagulation detector design by using optical and impedance methods, which can measure whole blood coagulation time accurately. In addition, we integrated the wireless transmission technologies with the proposed detector for long-distant caring and monitoring applications. This detector can detect the coagulation time at any time and any place for point-of-care testing (POCT). The cost of blood coagulation detector in hospital and commercial products are very expensive, which is not suitable for personal use or home use. We provide and fabricate a whole blood coagulation detector using the optical method.
    This instrument is based on the method of light transmittance to measure precisely the coagulation time according to the maximum accelerated point from the first-order differential curves. The optical detection uses the microprocessor TI MSP430F149, which includes 12-bit analog-to-digital converter (ADC) to control, to convert signals, and perform digital signal processing. By using high sensitivie optical-detecting sensors, analog filters, and digital filter, the detecting results can be optimized. Meanwhile, we use another common impedance method to compare. This method uses the impedance analyzer to determine the coagulation time according to first-order differential curve. This thesis investigates the optimal frequency for impedance method.
    To verify the reliability in this system, we performed the experiments for 40 times and the results are repeatable with the coefficient of variation (CV) =2.29%. The clinical experiments are based on 167 tubes of whole blood, and each tube is repeated twice in warm house at 37 Celsius degrees. We took the result of the first time to do statistic analysis. From the clinical experiment results, the accuracy and stability of this instrument were validated by testing 167 experiments. The correlated coefficients of the prothrombin time (PT) are 0.956 between the instrument and the hospital blood analyzer (ACL TOP).
    This thesis also dicover that the coagulation signals are affected by RBC, Fib, and Hct, and statistics between the coagulation signals and CBC are performed. The result shows that the slope at the maximum accelerated point in the first and second experiments are highly related with Fib。Thus, this device has advantages of portability, low cost for commercial mass marketing, easy operation, straightforward detection of whole blood and Bluetooth wireless transmission for long distance health care.

    第一章 緒論 1 1.1 凝血檢測儀研究背景與動機 1 1.2 重點照護檢驗 2 1.3 血液凝固機制簡介 5 1.4 凝血功能量測方法 7 1.5 系統軟硬體設計 10 1.6 臨床數據分析 11 1.7 論文架構 12 第二章 光檢測法及電阻抗分析法原理 15 2.1 光檢測法原理 15 2.1.1 透光度法與折射光法比較 15 2.1.2 光學原理 16 2.1.3 血液凝結影響透光度原因 18 2.1.4 血液中物質影響透光度的原因 24 2.2 電阻抗分析法原理 25 2.2.1 電阻抗分析法原理介紹 25 2.2.2 柯爾柯爾圖 26 2.2.3 波德圖 28 2.2.4 電極擴散現象 29 2.2.5 電阻抗法測量凝血 30 2.2.6 電極影響 32 第三章 系統介紹 34 3.1 光學檢測系統簡介 34 3.2 光學檢測系統實作 35 3.2.1 光檢測端 35 3.2.2 光發射器 36 3.2.3 光檢測元件 37 3.2.4 負阻抗電路 41 3.2.5 光二極體與光電晶體電路 45 3.2.6 三種光檢測器配合電路比較 46 3.2.7 微流道設計 51 3.2.8 穩壓器介紹 52 3.2.9 MSP430F149微控制器介紹 53 3.2.10 類比濾波器設計 55 3.2.11 時間模組 60 3.2.12 顯示模組 61 3.2.13 藍芽模組 62 3.2.14 系統實作 64 3.3 電阻抗系統介紹 65 3.3.1 電阻抗檢測端介紹 65 3.3.2 阻抗測量晶片AD5933 66 3.3.3 以AD5933測量阻抗 68 第四章 血液實測及效能改進 69 4.1 光學檢測實測 69 4.1.1 實驗架設 69 4.1.2 光檢測實驗流程 70 4.1.3 血液凝結時光檢測凝血訊號的轉折點 71 4.1.4 光學檢測正常血液 74 4.1.5 改變實驗用凝劑 76 4.1.6 數位濾波及PT值判斷演算法 81 4.1.7 藍芽驗證驗證 87 4.1.8 變異度分析 88 4.2 電阻抗分析法實測 90 4.2.1 血液柯爾-柯爾-圖建立 90 4.2.2 量測凝血時阻抗值變化 92 第五章 臨床實驗及結果統計分析 100 5.1 光學檢測臨床實驗 100 5.1.1 實驗設置 100 5.1.2 實驗可重複性及不同人操作比較 101 5.1.3 臨床實驗結果 102 5.1.4 凝血訊號類型 107 5.1.5 RBC聚集現象實驗驗證 113 5.1.6 血液調整Hematocrit比例與Fibrinogen 118 5.1.7 血液CBC數據與凝血訊號統計分析 121 5.2 電阻抗分析實驗設置及結果分析 124 第六章 結論與未來展望 130 6.1 結論 130 6.1.1 光檢測法及電阻抗分析法原理 130 6.1.2 系統介紹 130 6.1.3 血液實測及效能改進 130 6.1.4 臨床實驗及結果統計分析 131 6.2 未來展望 132 6.2.1 臨床實驗分析 132 6.2.2 功耗驗證 132 6.2.3 系統優化 132 6.2.4 檢測區改進 133 6.2.5 使用IC實現阻抗分析法 133 6.2.6 凝血訊號模擬器 133 參考文獻 135

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