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基于椭偏技术的纳米薄膜弱物理信号解析及其应用研究
Alternative TitleAnalysis and application of weak physical signals of nano-thin films based on ellipsometry technique
王晨昱
Thesis Advisor徐鹏
2024-05-20
Degree Grantor中国科学院大学
Place of Conferral北京
Subtype博士
Degree Discipline一般力学与力学基础
Keyword椭偏测量技术 光谱椭偏仪 成像椭偏传感器 小分子弱相互作用 弱应力检测
Abstract

随着纳米薄膜材料在生物医学、材料工程、光学仪器等诸多学科领域的快速发展,其在生物学、力学等诸多方面曾被忽略的弱物理信息逐渐成为研究的重点。譬如被广泛应用于疾病检测的生物芯片,它根据生物分子间特异性相互作用的原理,将生化分析过程集成于固相载体表面。为了实现对芯片信息的完整表达,需要通过对表面的超薄生物薄膜进行检测分析,然而对于接近传统测量极限甚至低于测量极限的待测浓度或弱相互作用,准确的测量解析仍具有挑战性。同样,在力学领域,随着高精尖重大科学装置以及高精密光学系统的发展,光学镀膜器件的性能指标有了显著提升,这就对其制造和组装过程中的应力性能标准提出了更高的要求。虽然现有的基于光学检测的应力测量技术已能够对熔融石英、玻璃等透明材料进行高精度的应力检测,但是针对更常见的金属和合金镀膜材料的残余应力高精度测量方案仍然有待进一步的开发。因此,如何实现纳米薄膜中的弱物理信号的准确解析成为本论文中亟需解决的关键科学问题。为此,本研究基于椭偏测量技术,针对不同的待测物理信息构建了对应检测模型。进一步通过提升检测灵敏度实现弱物理信号的有效解析。

本文首先结合光谱椭偏仪(SE) 和成像椭偏仪生物传感器(IEB) ,对不同浓度梯度的蛋白质分子相互作用过程进行定量化检测。对配基固定以及靶标识别两个过程通过准一阶动力学方程建立了统一的分析模型,得到了椭偏信号增量与蛋白芯片浓度的定量关系。并且通过对成像椭偏偏振设置进行优化固定,克服了作为生物传感器调节繁琐的使用限制。在优化的偏振方位角下完成验证实验,根据配体分子的特性构建传感表面,通过微流道反应系统实现配体分子的固定和不同浓度目标分子的吸附。结果表明定量模型成功验证了配基固定和靶标识别过程,并对蛋白质相互作用的亲和力大小进行定量解析,构建了完整的蛋白质定量测量体系。

进一步为满足小分子弱相互作用的检测需求,本文对基于PCSA布局的全内反射成像椭偏仪的生物传感器(TIRIE) 进行工作位点的优化,通过对偏振器件方位角的设置,得到了探测信号对界面微小扰动(界面电荷密度变化) 的响应;结果表明在非零线性条件下,椭偏探测信号对10-3μm-2量级的界面电荷密度扰动的响应相较于传统零位条件下提升了100倍。在此工作条件下,本文构建了一个全新的生物传感表面,将含有磺酸基团的钾盐分子作为配体固定在金薄膜基板上,然后将溶菌酶(LZM) 及其阴性对照传递到表面与磺酸基团发生静电相互作用。通过TIRIE生物传感器记录相互作用过程,得到表面灰度的实时测量曲线,并解析得到解离常数为2.63×10-5M,符合弱相互作用。结果表明了优化后的TIRIE生物传感器对小分子量生物互作的检测能力。

通过对薄膜光学常数的分析也可以实现应力信号的检测。本文第三部分的工作推导验证了椭偏测量技术在检测金属薄膜表面残余应力方面的可行性。对于单轴压缩薄膜,在p偏振光和s偏振光可以独立反射的情况下,使用常规椭圆偏振参数成功推导得到样品界面信息。在优化后的检测条件下,椭偏振幅ψ的应力灵敏度达到 kPa量级。结果表明椭偏响应来自应变引起的介电常数变化。本文建立了一个初步的微观模型来推导金属镀膜的介电常数变化与单轴拉伸应变s之间的关系。并提出椭偏测量系统可以作为一种替代方法来检测带有金属涂层的高精度光学器件的残余应力,对指导后续器件镀膜的设计和加工具有重要的实用价值。

Other Abstract

With the rapid advancement of nano-thin film materials across various fields such as biomedicine, materials engineering, and optical instrumentation, etc., the weak physical signal which had been neglected in many aspects such as biology and mechanics has gradually become the focus of research. For instance, biochips, which are widely used in disease detection, integrate biochemical analysis processes on the surface of solid phase carriers based on the principle of specific interactions between biomolecules. To achieve the complete expression of the chip information, it is necessary to detect and analyze the ultra-thin biofilm on the surface. However, it is still challenging to achieve accurate measurement and analysis in the face of some measured concentrations or weak interactions that are close to or even lower than the traditional measurement limit. Similarly, in the field of mechanics, with the development of sophisticated major scientific devices and high-precision optical systems, the performance indicators of optical coating devices have been significantly improved, which puts higher requirements on the stress performance standards in their manufacturing and assembly processes. Although the existing stress measurement technology based on optical detection has been able to detect the stress of transparent materials such as fused quartz and glass with high precision, the residual stress measurement scheme for the more common metal and alloy coating materials still needs to be further developed. Therefore, how to achieve accurate analysis of weak physical signals in nanofilms has become a key scientific problem that needs to be solved in this paper. Therefore, based on the ellipsometry technique, we construct corresponding detection models for different physical information to be measured. The weak physical signal can be effectively resolved by improving the detection sensitivity.

In this study, we employed spectroscopic ellipsometry (SE) and imaging ellipsometry biosensor (IEB) techniques to quantitatively assess protein molecule interactions across varying concentration gradients. A unified analysis model was established for ligand fixation and target identification processes through quasi-first-order kinetic equations, and the quantitative relationship between the ellipsometry signal increment and protein chip concentration was obtained. Moreover, by optimizing and fixing the imaging ellipsometry setting, the cumbersome limitation of using as a biosensor is overcome. The verification experiment was completed under the optimized polarization azimuth, and the sensing surface was constructed according to the characteristics of ligand molecules, and the fixation of ligand molecules and the adsorption of target molecules with different concentrations were realized through the microchannel reaction system. The results showed that the quantitative model successfully verified the process of ligand fixation and target recognition, and quantitatively analyzed the protein interaction size, and built a complete protein quantitative measurement system.

Additionally, to cater to the detection requirements of weak affinity interaction of small molecules, the working site of the total internal reflection imaging ellipsometry (TIRIE) based on PCSA layout is optimized. By setting the azimuth of the polarization device, the response of the detection signal to the small disturbance of the interface (the change of the optical constant of the film layer) is obtained. The results show that the response of ellipsometry signal to the disturbance of the interfacial charge density in the order of 10-3μm-2 is 100 times better than that of the traditional null condition. Under this working condition, a new biosensing surface was constructed, which fixed potassium salt molecules containing sulfonic acid groups as ligands on the gold thin film substrate, and then transferred lysozyme (LZM) and its negative control to the surface for electrostatic interaction with sulfonic acid groups. The interaction process was recorded by TIRIE biosensor, and the real-time measurement curve of surface gray level was obtained. The dissociation constant was 2.63×10-5M, which was consistent with the weak interaction. The results show that the optimized TIRIE biosensor can detect small amount of weak interaction.

Furthermore, ellipsometry also proves beneficial in detecting weak stress signals in high-precision optical devices with metal coatings. In the third part of this study, the feasibility of ellipsometry measurement in detecting residual stress on the surface of metal films is verified. For uniaxial compression films, the interface information of the sample is derived successfully by using conventional ellipsoid parameters when p-polarized light and s-polarized light can be reflected independently. Under the optimized detection conditions, the stress sensitivity of the ellipsometry amplitude ψ reaches kPa. The results show that the ellipsometry response comes from the variation of dielectric constant induced by strain. In this paper, a preliminary microscopic model is established to deduce the relationship between the change of dielectric constant of metal coating and the uniaxial tensile strain s. The ellipsometry measurement system can be used as an alternative method to detect the residual stress of high precision optical devices with metal coating, which has important practical value to guide the subsequent device coating design and processing.

Language中文
Document Type学位论文
Identifierhttp://dspace.imech.ac.cn/handle/311007/95221
Collection微重力重点实验室
Recommended Citation
GB/T 7714
王晨昱. 基于椭偏技术的纳米薄膜弱物理信号解析及其应用研究[D]. 北京. 中国科学院大学,2024.
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