高频电磁场对悬液中细胞膜电位影响的理论研究与实时电磁辐照装置设计

发布时间：2019-02-19 08:57

【摘要】：电磁辐射对健康的影响引起了广泛关注,电磁辐射生物效应研究是评估电磁辐射潜在健康危害的有效方式。一方面,研究表明,细胞膜可能是外加电磁场作用的初始靶标,细胞膜上的跨膜电位等相关电生理信号是人们关注的重点。细胞膜电位是反映细胞生理状态和功能的良好指标,而在外加电磁场的作用下,细胞膜电位的变化可能会引起细胞生理、生化状态的改变,进而导致后续一列的连锁反应。另一方面,已有的电磁辐射生物效应研究多集中于辐照后的生物学效应,即在电磁辐射之后的某些时间点检测生物样本相关指标的变化情况,忽略了辐照过程中的效应。而电磁场对生物体电生理信号的作用很可能是一个实时的作用,可通过生物体电生理信号的改变而导致后续一系列变化如神经递质紊乱、基因表达改变等。但由于缺乏实时的电磁辐照系统,相关研究尚无法开展。因此,基于以上两方面,建立外加电磁场作用下细胞膜电位计算模型,设计基于细胞电生理记录的实时电磁辐照装置对掌握细胞膜电位的变化规律、开展电磁辐射过程中的生物效应研究及其在生物、医学领域的应用具有重要指导意义。且两部分内容相辅相成,膜电位的理论计算模型研究为预测可能的电磁辐射生物效应提供理论依据;适用于细胞电生理记录的实时电磁辐照装置又作为检测细胞电信号的基础,为理论计算模型提供验证手段。综合以上两方面的考虑,本文首先建立了外加电磁场作用下,悬液细胞膜电位的理论计算模型,并将模型的适用范围扩展到高频电磁场,尤其是频率高于细胞膜弛豫频率的情况。随着频率的升高,细胞膜的电导率和细胞膜内外的电容特性均需考虑在计算模型中,本文通过有效介质理论和场近似等效的方法将悬液中其他细胞的影响等效于一个局部场的作用,利用已经建立的外电场作用下单个细胞膜电位的计算模型推导出外加高频电磁场作用下,悬液细胞膜电位的计算模型。计算结果表明:在频率较低时,悬液细胞膜电位受频率、细胞浓度、排列方式等因素的影响,而当频率较高时,频率上升为主导因素。由于细胞内、外液的介电弛豫效应,跨膜电位没有随着频率升高而单调的下降,而是在中间某个频段出现了平台效应,之后随频率继续上升膜电位再重新下降。最后与其他类似的计算模型(低频)以及数值计算结果进行对比,分析了理论计算模型与数值计算结果存在偏差的原因——有效介质理论和场近似等效的方法不能精确的计算出悬液中局部电势/场分布。并提出了一种基于Bergman谱理论的可能解决方法。实际上,建立外加电场作用下悬液中细胞膜电位的理论计算模型,其关键在于精确的计算出细胞悬液的局部电场或电势分布,我们将非均质细胞单壳模型等效为均质小球模型后,实质上细胞悬液就转化成了一个二元复合介质,而基于Bergman谱理论的方法正好可以精确的计算复合介质中的电场和电势分布。第二部分内容,首先根据生物实验的需要,确定电磁辐照装置的结构为开放式传输线结构,并得到传输线结构的尺寸约束条件;然后针对阻抗匹配、单模传播等电磁特性要求,确定电磁辐照装置的结构为微屏蔽共面波导。利用保角变换法推导了微屏蔽共面波导的结构尺寸与特征阻抗关系的解析式,再结合已有的尺寸约束条件初步确定了微屏蔽共面波导的结构尺寸参数。通过CST电磁仿真软件分别建立了无生物样本和有生物样本两种情况下的微屏蔽共面波导电磁仿真模型,得到了无生物样本模型的S参数、场分布以及有生物样本模型的SAR分布及其均匀性等关键性参数。针对细胞悬液中凹液面对SAR分布的影响,又建立了含凹液面的培养皿模型,对比了平液面和凹液面的SAR分布情况,仿真结果显示凹液面对SAR分布具有明显影响。针对生物样本SAR均匀性问题,提出了改变激励方式的方法——由一端激励变为两端同时激励,仿真结果表明生物样本的SAR的均匀性有较大改善。针对电磁干扰问题,拟采用改变电极插入角度、延长玻璃电极长度等多种方式减少电磁场对电极的干扰。最后,由于MEMS技术加工微屏蔽共面波导的尺寸限制和成本问题,提出了一种新的加工工艺流程,将微屏蔽共面波导分成两部分,通过PCB加工和机械加工后再组合的方式解决了微屏蔽共面波导的加工制造问题。综上,电磁仿真结果表明设计方法合理、可靠,设计的未屏蔽共面波导装置完全符合电磁和生物实验的两方面要求,并且各参数性能较目前已有的照射装置更好。考虑到整个照射系统组建、调试和膜片钳实验的复杂性,仍需生物实验验证,这部分工作将在今后开展。
[Abstract]:The effects of electromagnetic radiation on the health of electromagnetic radiation are of great concern, and the biological effect of electromagnetic radiation is an effective way to evaluate the potential health hazards of electromagnetic radiation. On the one hand, the research shows that the cell membrane may be the initial target of the applied electromagnetic field, and the transmembrane potential and other related electrophysiological signals on the cell membrane are the focus of attention. The potential of the cell membrane is a good index to reflect the physiological state and function of the cell, and under the effect of the applied electromagnetic field, the change of the cell membrane potential can cause the change of the physiological and biochemical state of the cell, thus leading to a chain reaction in the subsequent column. On the other hand, the existing biological effect of electromagnetic radiation has focused on the biological effect after irradiation, that is, the change of the relevant index of the biological sample is detected at some time points after the electromagnetic radiation, and the effect in the irradiation process is ignored. The effect of the electromagnetic field on the electrophysiological signal of the living body is likely to be a real-time function, which can lead to a subsequent series of changes, such as neurotransmitter disturbance, gene expression change, and the like, by the change of the biological electrophysiological signal. However, due to the lack of a real-time electromagnetic radiation system, the relevant research can not be carried out. therefore, based on the above two aspects, a cell membrane potential calculation model is established under the action of an external electromagnetic field, The application of the medical field is of great guiding significance. and the theoretical calculation model of the membrane potential is used for providing a theoretical basis for predicting the potential electromagnetic radiation biological effect; and the real-time electromagnetic irradiation device is suitable for the cell electrophysiology recording as a basis for detecting the cell electric signal, and provides a verification means for the theoretical calculation model. In the light of the above two aspects, the theoretical calculation model of the membrane potential of the suspension liquid under the action of the applied electromagnetic field is first established, and the application range of the model is extended to the high-frequency electromagnetic field, in particular, the frequency is higher than the relaxation frequency of the cell membrane. With the increase of frequency, the electrical conductivity of the cell membrane and the capacitance characteristics inside and outside the cell membrane need to be taken into account in the calculation model. The effect of the other cells in the suspension liquid is equivalent to the effect of a local field by means of the effective medium theory and the field approximation equivalent method. The calculation model of the membrane potential of the suspension liquid under the action of an external high-frequency electromagnetic field is derived by the calculation model of the potential of a single cell membrane under the action of an external electric field which has been established. The results show that, when the frequency is low, the cell membrane potential is affected by the factors such as frequency, cell concentration, arrangement mode and so on, and when the frequency is higher, the frequency increases as the leading factor. Due to the dielectric relaxation effect of the internal and external liquid, the transmembrane potential does not decrease monotonically with the increase of frequency, but the platform effect occurs in a certain frequency band in the middle, and then the film potential continues to decrease with the frequency. Finally, compared with other similar calculation models (low frequency) and numerical results, the reason that the deviation between the theoretical calculation model and the numerical result is analyzed. The effective medium theory and the field approximate equivalent method cannot accurately calculate the local electric potential/ field distribution in the suspension liquid. and a possible solution based on Bergman spectral theory is proposed. In fact, a theoretical calculation model for the potential of the cell membrane in the suspension liquid under the action of an external electric field is established, the key point is to accurately calculate the local electric field or the potential distribution of the cell suspension liquid, and after the non-homogeneous cell single-shell model is equivalent to a homogeneous pellet model, In essence, the cell suspension is transformed into a binary composite medium, while the method based on the Bergman spectrum theory can accurately calculate the electric field and the potential distribution in the composite medium. in the second part, firstly, according to the needs of the biological experiment, the structure of the electromagnetic radiation device is determined to be an open transmission line structure, and the size constraint condition of the transmission line structure is obtained; and then, aiming at the requirements of electromagnetic characteristics such as impedance matching, single mode propagation, and the like, the structure of the electromagnetic radiation device is determined to be a micro-shielded coplanar waveguide. The analytical formula of the relation between the structure and the characteristic impedance of the micro-shielded coplanar waveguide is derived by the conformal transformation method, and the structural dimension parameters of the micro-shielded coplanar waveguide are preliminarily determined by combining the existing size constraints. The electromagnetic simulation model of the micro-shield coplanar waveguide in the condition of no biological sample and biological sample is established by the CST electromagnetic simulation software, and the critical parameters such as the S parameter, the field distribution and the SAR distribution and the uniformity of the biological sample model are obtained. The effect of the concave liquid level on the distribution of the SAR in the cell suspension is also established, and the model of the culture dish containing the concave liquid level is established, and the SAR distribution of the flat surface and the concave liquid surface is compared. The simulation results show that the concave liquid level has a significant effect on the SAR distribution. In order to solve the problem of the uniformity of the biological sample, the method of changing the excitation mode is proposed. The excitation of one end becomes the simultaneous excitation at both ends, and the simulation results show that the uniformity of the SAR of the biological sample is greatly improved. aiming at the problem of electromagnetic interference, the interference of the counter electrode of the electromagnetic field can be reduced by changing the insertion angle of the electrode, prolonging the length of the glass electrode and the like. in the end, due to the size limitation and the cost problem of the micro-shield coplanar waveguide processed by the MEMS technology, a new processing flow is proposed, and the micro-shielded coplanar waveguide is divided into two parts, and the processing and manufacturing problems of the micro-shielded coplanar waveguide are solved by a combination of the PCB processing and the machining. The results of the electromagnetic simulation show that the design method is reasonable and reliable, and the design of the non-shielded coplanar waveguide device is in full compliance with the two aspects of the electromagnetic and biological experiments, and the performance of each parameter is better than that of the existing illumination device. In view of the complexity of the whole illumination system formation, commissioning and patch clamp experiments, it is still necessary to verify that this part of the work will be carried out in the future.
【学位授予单位】：中国人民解放军军事医学科学院
【学位级别】：博士
【学位授予年份】：2015
【分类号】：R594.8

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