【摘要】：糖尿病是一種嚴重危害人類健康的重大疾病，目前還沒有根治的手段。為了有效地降低并發(fā)癥的發(fā)病率，需要對血糖進行頻繁測量。實現(xiàn)血糖水平的無創(chuàng)傷、連續(xù)測量具有重要的現(xiàn)實意義。 中紅外（Mid-Infrared，MIR）光譜對分子的選擇性好，不同分子之間的光譜重疊和干擾不嚴重，信息豐富。中紅外光譜無創(chuàng)血糖測量方法研究已經(jīng)開展了很多年，但一直沒有得到突破性的研究成果。該方法所面臨的主要問題在于：a)缺乏對中紅外光譜無創(chuàng)血糖測量方法中存在的光與生物組織的相互作用、葡萄糖的來源、光譜與血糖之間的關(guān)系等問題的細致研究，因此，也缺乏提高分析結(jié)果精度的有效手段。b)人體皮膚是一復(fù)雜、時變的系統(tǒng)，其光譜易受到一些物理、化學(xué)因素的干擾，會直接影響定標模型的可靠性與穩(wěn)健性。c)與血糖有關(guān)的吸收信號非常微弱，給信息的提取帶來了困難。 本文對中紅外光譜無創(chuàng)血糖測量方法中存在的上述問題進行了研究，主要內(nèi)容如下： 1）對中紅外光譜無創(chuàng)血糖測量方法中存在的光與生物組織的相互作用、皮膚光譜中與血糖有關(guān)的吸收信息來源、組織液中葡萄糖含量與血糖水平的關(guān)系等問題進行了分析，提出利用中紅外光譜測量表皮組織液中葡萄糖含量來實現(xiàn)血糖無創(chuàng)傷測量的物理模型。與分析血液信息相比，組織液光譜中不存在血紅蛋白等生化成分的干擾，較容易實現(xiàn)無創(chuàng)傷血糖測量。 2）對中紅外光譜分析組織液中葡萄糖的定標方法進行了研究。中紅外光譜分析技術(shù)中的化學(xué)計量學(xué)信息提取方法直接影響測量結(jié)果的精度與可靠性。本文研究結(jié)果表明，分析組織液中葡萄糖含量時，偏最小二乘回歸（Partial Least Squares Regression，PLSR）方法能獲得較好的測量結(jié)果。 3）利用膠帶粘貼、水沖洗及打磨等方式分別對皮膚進行預(yù)處理，研究皮膚預(yù)處理方式對其衰減全反射(Attenuated Total Reflection,ATR)紅外光譜的影響，并分析造成這種影響的機制。結(jié)果表明，光程變化是導(dǎo)致皮膚光譜變化的主要原因。當(dāng)光程變化信息與葡萄糖的濃度信息之間存在偶然相關(guān)時，所得PLSR模型的分析精度與穩(wěn)健性都會受到影響；利用附加散射校正（Multiplicative Scatter Correction，MSC）、變量標準化（StandardNorrmalized Variate，SNV）方法對可以對光譜中的光程信息進行校正。 4）根據(jù)PLSR算法原理，提出了評估光譜干擾因素對定標結(jié)果影響的方法；結(jié)合具體實驗，對中紅外光譜無創(chuàng)血糖測量方法中存在的光譜測量時機、角質(zhì)層的吸收變化、接觸壓力等干擾因素影響進行研究。并通過口服葡萄糖耐量實驗（Oral Glucose Tolerance Test，，OGTT）實驗，發(fā)現(xiàn)表皮中的組織液很難滲透到皮膚角質(zhì)層中進而被倏逝波所探測到。 5）提出了中紅外光譜無創(chuàng)血糖測量系統(tǒng)的物理設(shè)計方案，對提高光譜信噪比的技術(shù)手段進行了分析。通用的光譜儀不能滿足中紅外無創(chuàng)血糖測量的要求，基于可調(diào)諧量子級聯(lián)光器激(Quantum Cascade Laser,QCL)光源的光譜測量系統(tǒng)物理設(shè)計方案能有效提高所得皮膚光譜的信噪比，有助于實現(xiàn)血糖的無創(chuàng)傷測量。
[Abstract]:Diabetes mellitus is a major disease that seriously endangers human health. There is no radical cure at present. In order to effectively reduce the incidence of complications, it is necessary to measure blood sugar frequently.
Mid-Infrared (MIR) spectroscopy has good selectivity to molecules, and the overlap and interference between different molecules are not serious, and the information is abundant. There are many problems in the non-invasive measurement of blood glucose by external spectroscopy, such as the interaction between light and biological tissue, the source of glucose, the relationship between spectrum and blood glucose. Therefore, there is no effective means to improve the accuracy of the analysis results. b) Human skin is a complex, time-varying system, and its spectrum is susceptible to some physical and chemical factors. Interference will directly affect the reliability and robustness of the calibration model. c) The absorption signal related to blood glucose is very weak, which makes it difficult to extract information.
In this paper, the problems in the non-invasive measurement of blood glucose by mid-infrared spectroscopy are studied.
1) The interaction between light and biological tissues, the source of absorption information related to blood glucose in skin spectra, the relationship between glucose content in tissue fluid and blood glucose level were analyzed. The method of measuring glucose content in epidermal tissue fluid by mid-infrared spectroscopy was proposed. Physical model of non-invasive measurement. Compared with the analysis of blood information, there is no interference of hemoglobin and other biochemical components in tissue-fluid spectra, so it is easier to achieve non-invasive blood glucose measurement.
2) The calibration method of glucose in tissue fluids by mid-infrared spectroscopy is studied. The stoichiometric information extraction method in mid-infrared spectroscopy directly affects the accuracy and reliability of measurement results. Ression (PLSR) method can get better results.
3) The skin was pretreated by adhesive tape, water washing and polishing, and the effect of skin pretreatment on ATR infrared spectra was studied, and the mechanism of the effect was analyzed. When there is an accidental correlation between chemical information and glucose concentration information, the analytical accuracy and robustness of the PLSR model will be affected, and the optical path information in the spectrum can be corrected by using the method of Multiplicative Scatter Correction (MSC) and Standard Norrmalized Variate (SNV).
4) According to the principle of PLSR algorithm, a method for evaluating the influence of spectral interference factors on the calibration results is proposed. Combined with specific experiments, the influence of spectral measurement timing, cuticle absorption changes, contact pressure and other interference factors in the non-invasive mid-infrared blood glucose measurement method is studied. Coste Tolerance Test (OGTT) showed that it was difficult for tissue fluids in the epidermis to penetrate into the cuticle and be detected by evanescent waves.
5) The physical design scheme of the mid-infrared noninvasive blood glucose measurement system is proposed, and the technical means to improve the signal-to-noise ratio of the spectrum are analyzed. The case can effectively improve the signal to noise ratio of the obtained skin spectrum, and help to achieve the non-invasive measurement of blood sugar.
【學(xué)位授予單位】：暨南大學(xué)
【學(xué)位級別】：博士
【學(xué)位授予年份】：2012
【分類號】：R318.0

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1 楊皓e

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