本文關(guān)鍵詞： QCM免疫傳感技術(shù) 復(fù)合諧振器 質(zhì)量靈敏度 宮頸癌　出處：《電子科技大學(xué)》2016年博士論文　論文類型：學(xué)位論文

【摘要】：石英晶體微天平(Quartz Crystal Microbalance)是一種新型高靈敏度的質(zhì)量傳感器,由于其具有結(jié)構(gòu)簡(jiǎn)單、成本低、檢測(cè)速度快、測(cè)量精度可以達(dá)到納克量級(jí)等優(yōu)點(diǎn),被廣泛的應(yīng)用于物理、化學(xué)、生物、醫(yī)學(xué)等各個(gè)領(lǐng)域。QCM免疫傳感器結(jié)合了QCM的高靈敏度和免疫反應(yīng)的特異性,獲得了研究人員的廣泛關(guān)注,被廣泛的應(yīng)用于包括環(huán)境檢測(cè)、食品安全、醫(yī)學(xué)疾病診斷等各個(gè)領(lǐng)域。宮頸癌是所有女性疾病中致死率排名第二的惡性腫瘤,而在所有的惡性腫瘤中,宮頸癌也是最容易預(yù)防的惡性腫瘤�；颊呷绻趯m頸癌的癌前病變時(shí)期得到了及時(shí)治療,治愈的機(jī)會(huì)非常高,但該時(shí)期沒(méi)有明顯的臨床癥狀,如果僅僅依靠臨床表現(xiàn)無(wú)法對(duì)宮頸癌前病變進(jìn)行診斷,而一旦宮頸癌前病變發(fā)展到浸潤(rùn)癌,病人一般會(huì)在2-5年的時(shí)間內(nèi)死亡。因此,發(fā)展一種特異性強(qiáng)、靈敏度高的宮頸癌變前檢測(cè)手段對(duì)宮頸癌的預(yù)防舉足輕重。本文以壓電免疫傳感技術(shù)為基礎(chǔ),通過(guò)深入研究壓電免疫傳感器的檢測(cè)機(jī)理,提出了一種宮頸癌變前檢測(cè)的新方法。通過(guò)深入分析各種影響徑向質(zhì)量檢測(cè)靈敏度的因素,搭建了適合宮頸癌變前檢測(cè)的實(shí)驗(yàn)平臺(tái)并設(shè)計(jì)了最適合該平臺(tái)的實(shí)驗(yàn)方法,將該方法用于臨床病人樣本的檢測(cè),驗(yàn)證了該方法在宮頸癌變前檢測(cè)中的合理性和有效性。本文的主要工作及創(chuàng)新點(diǎn)總結(jié)如下:(1)深入的分析了石英晶體微天平的檢測(cè)機(jī)理,揭示了其具有高檢測(cè)靈敏度的原因,同時(shí),深入分析了石英晶體微天平表面振動(dòng)位移分布情況,并以此為基礎(chǔ),詳細(xì)研究了電極的半徑、厚度及形狀對(duì)石英晶體微天平質(zhì)量檢測(cè)靈敏度分布的影響,提出了提高質(zhì)量檢測(cè)靈敏度及改善質(zhì)量檢測(cè)靈敏度均勻性的方法,為石英晶體微天平的應(yīng)用提供了理論基礎(chǔ)。(2)研究了針對(duì)宮頸癌變前檢測(cè)的特異性傳感膜的制備方法。詳細(xì)分析了各種特異性傳感膜的制備方法,并通過(guò)實(shí)驗(yàn)從固化率、穩(wěn)定性及免疫活性等各個(gè)方面對(duì)各種不同方法進(jìn)行了比較,同時(shí)研究了環(huán)境溫度、培育時(shí)間及抗體濃度等對(duì)傳感膜固化率、穩(wěn)定性及免疫活性的影響,最后提出了最適合用于宮頸癌變前檢測(cè)的特異性傳感膜制備方法及制備條件。(3)提出了一種基于QCM的宮頸癌變前檢測(cè)的新方法。通過(guò)將該方法用于從四川大學(xué)華西附屬第二婦女兒童醫(yī)院獲得的病人樣本的檢測(cè)發(fā)現(xiàn),被測(cè)樣本中P16~(INK4a)蛋白的含量和宮頸病變程度密切相關(guān),病變程度越高,P16~(INK4a)蛋白含量越高,反之,病變程度越低,P16~(INK4a)蛋白含量就越少,并且在不同的病變程度之間,P16~(INK4a)蛋白的含量有明顯的差異(p0.05),具有統(tǒng)計(jì)學(xué)意義。因此,通過(guò)檢測(cè)樣本中P16~(INK4a)蛋白的含量可確定被測(cè)對(duì)象的宮頸病變程度。通過(guò)將該方法的檢測(cè)結(jié)果和病理醫(yī)生的活檢切片檢查結(jié)果對(duì)比發(fā)現(xiàn),該方法確定的病人病變程度和活檢檢測(cè)結(jié)果吻合度高。最后,本文還對(duì)該方法的特異性、穩(wěn)定性、檢測(cè)下限等性能進(jìn)行了測(cè)試,為該方法的臨床研究提供了基礎(chǔ)。
[Abstract]:Quartz crystal microbalance (Quartz Crystal Microbalance) is a new kind of sensor with high sensitivity, because of its simple structure, low cost, fast detection speed, the measurement accuracy can reach nanogram level has been widely used in physics, chemistry, biology, medical field and other.QCM immunosensor combined with high specificity the sensitivity and the immune response of QCM, get the attention of many researchers, has been widely used in environmental detection, food safety, medical field disease diagnosis. Cervical cancer is the malignant tumor mortality rate ranked second of all female diseases, and in all the malignant tumors, cervical cancer is the most preventable the malignant tumor patients. If in the period of cervical cancer precancerous lesions got timely treatment, the chances are very high, but this time no obvious clinical symptoms, if only Based on clinical manifestations unable to diagnosis cervical precancerous lesions, and once the cervical precancerous lesions to the development of invasive carcinoma, patients often die within 2-5 years. Therefore, the development of a strong specificity and high sensitivity of cervical cancer prevention and detection methods of cervical cancer before the pivotal. On the basis of piezoelectric immunosensing technique, the detection mechanism of piezoelectric immunosensor through in-depth research, put forward a new method for the detection of cervical precancerous. Through in-depth analysis of various factors affecting the quality of radial detection sensitivity, to build an experimental platform for the detection of cervical cancer before change and design method is the most suitable for the platform, will the method for the detection of clinical samples of patients, the validation of the method in cervical cancer before the test is reasonable and effective. The main work and innovation points are summarized as follows: (1) in-depth analysis The detection mechanism of the quartz crystal microbalance, reveals its reason, high detection sensitivity at the same time, in-depth analysis of the surface displacement distribution of quartz crystal microbalance, and on this basis, a detailed study of the electrode radius, thickness and shape of quartz crystal micro balance quality detection sensitivity distribution, put forward to improve the quality of the detection sensitivity and improve the quality of detection sensitivity and uniformity of the method, and provides the theoretical basis for the application of quartz crystal microbalance. (2) studied the preparation method for the specific detection of cervical precancerous sensing film. A detailed analysis of the preparation of a variety of specific sensor membrane, and through the experiment from the curing rate the stability and immune activity, and other aspects of the comparison of different methods, and the effects of environment temperature, incubation time and antibody concentration on the sensing membrane curing rate, stability Effect and immune activity, and finally put forward the most suitable for cervical cancer before the specific detection sensing membrane preparation method and preparation conditions. (3) proposed a new method for the detection of cervical cancer QCM. Based on the detected by this method is used to obtain from the women and children hospital of Sichuan University affiliated Huaxi second the patient sample, the measured samples of P16~ (INK4a) is closely related to the protein content and the degree of cervical lesions, the higher the degree of lesion, P16~ (INK4a) protein content is high, on the contrary, the lower the degree of lesion, P16~ (INK4a) protein content was lower, and between the lesions in different degrees, (P16~ INK4a) have significant differences in protein content (P0.05), with statistical significance. Therefore, the detection of P16~ in the sample (INK4a) protein content can determine the degree of cervical lesions. The object of the detection results and the method of biopsy pathology doctor Compared with the results of biopsy, the results showed that the degree of coincidence between the patients determined by the method and the biopsy results was high. Finally, the specificity, stability and detection limit of the method were tested, which provided a basis for clinical research of this method.

【學(xué)位授予單位】：電子科技大學(xué)
【學(xué)位級(jí)別】：博士
【學(xué)位授予年份】：2016
【分類號(hào)】：TP212;R737.33

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