【作者】 谭邹卿；

【导师】 张能辉；

【作者基本信息】 上海大学 ， 固体力学， 2013， 博士

【摘要】 利用微悬臂梁实验、聚合刷标度理论、DNA溶液液晶理论以及层合梁两变量方法等，研究温变效应和分子间相互作用对无标记生物检测中DNA-微弹性结构纳米力学响应的影响，构建DNA分子几何特征、缓冲溶液离子强度、非生物层力学性能以及温度变化等与DNA-微弹性结构挠度以及频率变化之间的关系。主要工作如下：(1)利用微悬臂梁光杠杆技术实时测量了DNA分子在种植和杂交过程中引起DNA-微梁挠度检测信号，考察了碱基对数以及温度变化对单链DNA(ssDNA)-微梁以及双链DNA(dsDNA)-微梁挠度检测信号的影响。研究表明：温度变化对DNA-微梁挠度检测信号的干扰不可忽略。(2)基于de Gennes的聚合刷标度理论和Zhang的层合梁两变量方法，利用能量最小原理建立了ssDNA-微梁纳米力学响应的能量模型，研究了碱基对数、种植密度以及温度变化对ssDNA-微梁挠度的影响，并与第二章的实验结果进行了对比，说明了构型熵是引起ssDNA-微梁纳米力学响应的重要因素，但还需考虑分子间其它相互作用(如静电力)的贡献。(3)借助Strey等提出的DNA液晶理论，考虑静电力、水合力以及构型熵三种微观作用对DNA-微梁挠度的影响，结合第二章等温情况下的实验数据，利用变分法得到的解析模型拟合了种植和杂交过程中DNA-微梁的物理化学参数，从理论上解释了DNA杂交引起微梁的上翘下弯现象，并预见了在DNA-微梁挠度差检测技术中存在失效现象，同时分析了DNA链间相互作用和溶液离子强度变化对检测失效的影响。(4)考虑非生物层的热弹性变形能以及DNA生物膜的自由能，建立了在力-热共同作用下的DNA-微梁挠度的解析模型，并与第二章温变情况下的实验结果进行了对比，证实了该能量模型的可靠性。给出了在不同种植密度、碱基对数、溶液离子强度以及基底材料条件下的温变控制条件，说明了DNA-微梁挠度差检测技术的热相关性。此外，根据连续介质力学观点理论预测了DNA生物膜热膨胀系数，说明了近表面系统(DNA-微梁)与渗透溶液系统的差异。(5)基于Hamilton原理建立了力-热作用下DNA-微梁动态响应的解析模型，研究了基底非生物层材料种类、DNA分子结构特性以及温度变化等对DNA-微梁动态响应的影响。研究表明：基底材料和吸附DNA分子种类对频率偏移的影响明显。大部分情况下DNA分子吸附使得DNA-微梁频率减小。然而，以SU8聚合物基底的dsDNA-微梁频率存在增加或减小现象。在种植密度大约为0.25#/nm2时，dsDNA-微梁频率几乎无变化，使得动态检测失效。此外，相比于静态工作模式，DNA-微梁动态工作模式具有更高的热稳定性。(6)利用变分法建立了力-热作用下DNA-圆薄板轴对称弯曲问题的理论模型，对比了本文提出的四层板模型预测结果与简化两层板模型结果，研究了温变效应对DNA-圆薄板挠度的影响。结果表明：需考虑PDMS层和钛层对DNA-圆薄板挠度的影响。温度变化对DNA-圆薄板挠度的影响不可忽略，应严格控制DNA-圆薄板的环境温变，特别在低种植密度、短链DNA分子以及高溶液离子强度条件下尤为如此。更多还原

【Abstract】 The microcantilever-based experiment, scaling theory of polymer brushes, liquid crystaltheory of DNA solution, two-variable method for laminated beams, etc., are utilized to investigatethe influences of thermal effect and intermolecular interactions on the nanomechanical responsesof DNA-microelastic structures in label-free biodetections. The relation between the deflection,resonance frequency shift of a DNA-microelastic structure and DNA molecular structure feature,ionic strength of buffer solution, mechanical properties of non-biological layers, temperaturechange, etc., is established. Main works are as follows:(1) Using optical lever technique based on a microcantilever sensor, the real-time deflections of aDNA-microcantilever during the immobilization and hybridization processes are measured.The influences of nucleotide number and temperature change on the deflection signals of aDNA(ssDNA or dsDNA)-microcantilever are investigated. This result shows the influence oftemperature change on the deflections of a DNA-microcantilever cannot be ignored.(2) Based on de Gennes’s scaling theory for polymer brushes and Zhang’s two-variable methodfor laminated beams, an energy model for nanomechanical motion of assDNA-microcantilever is presented. The effects of nucleotide number, grafting density, andtemperature change on deflections are discussed. The comparisons of numerical predictionsand experimental data from Chapter2suggest that, although the conformational entropy is animportant factor, it is necessary to investigate the influence of other intermolecularinteractions (e.g. electrostatic force) on deflections.(3) By means of Strey’s liquid crystal theory for DNA solutions, the contributions of threemicroscopic interactions including electrostatic force, hydration force, and conformationalentropy to the deflections of a DNA-microcantilever are discussed. The physico-chemicalparameters for a DNA-microcantilever during the immobilization and hybridizationprocesses are accomplished by curve fitting with the experimental data from Chapter2underisothermal conditions. This theoretical model elucidates the experimental phenomenon ofupward or downward motions induced by DNA hybridization. The proposed model alsopredicts that there exists a failure phenomenon, which will make the differential deflectiontechnique invalid. A failure analysis induced by interactions between DNA molecules andchange of ionic strengths is discussed.(4) Considering thermoelastic energy of non-biological layers and free energy of DNA biofilm,an analytical model for the deflections of a DNA-microcantilever is presented under thecombination of mechanical and thermal loadings. The predicted deflections are comparedwith the experimental data from Chapter2to validate the applicability of this model. Under different conditions (e.g. grafting density, nucleotide number, ionic strength of solution, andsubstrate material), the controlling temperature is obtained. And the thermal correlation ofDNA-microcantilevers is discussed. At the same time, the macroscopic thermal expansioncoefficient of a DNA biofilm on the basis of continuum mechanics viewpoints is obtained.The difference between the near-surface system (DNA-microcantilever) and the osmoticpressure solution system is discussed.(5) An analytical model is presented to predict the dynamical response of aDNA-microcantilever according to Hamilton’s principle. The effects of the sort of thematerial of non-biological substrate layer, DNA molecular structure features, and temperaturechange on the resonant frequency of a DNA-microcantilever are discussed. Results indicatethat the influences of substrate materials and types of DNA molecules on the resonantfrequency shift of a DNA-microcantilever are prominent. In most cases, the resonantfrequency of a DNA-microcantilever decreases with DNA adsorption. However, the resonantfrequency of a dsDNA-SU8-microcantilever exists increase or decrease. At the graftingdensity of0.25#/nm2, the resonant frequency of a dsDNA-SU8-microcantilever keeps almostno change, which makes the dynamical detection fail. In addition, compared to the staticmode of operation, the dynamic mode of a DNA-microcantilever has a higher thermalstability.(6) A variational method is presented to formulate an analytical model for the axisymmetricbending of a DNA-thin-circular-plate under the combination of axisymmetric mechanical andthermal loadings. The comparisons of the proposed four-layered plate model and the reducedtwo-layered plate model are discussed. The effect of temperature change on deflections of aDNA-plate is studied. Results show that the contribution of PDMS and Ti layers tonanomechanical deflections of a DNA-plate should be considered. As the influence oftemperature change on deflections of a DNA-plate cannot be ignored, the temperature changeshould be carefully controlled, especially at a low grafting density, with a small nucleotidenumber, and at a high ionic strength of solution.更多还原