【摘要】：電磁輻射對健康的影響引起了廣泛關注,電磁輻射生物效應研究是評估電磁輻射潛在健康危害的有效方式。一方面,研究表明,細胞膜可能是外加電磁場作用的初始靶標,細胞膜上的跨膜電位等相關電生理信號是人們關注的重點。細胞膜電位是反映細胞生理狀態(tài)和功能的良好指標,而在外加電磁場的作用下,細胞膜電位的變化可能會引起細胞生理、生化狀態(tài)的改變,進而導致后續(xù)一列的連鎖反應。另一方面,已有的電磁輻射生物效應研究多集中于輻照后的生物學效應,即在電磁輻射之后的某些時間點檢測生物樣本相關指標的變化情況,忽略了輻照過程中的效應。而電磁場對生物體電生理信號的作用很可能是一個實時的作用,可通過生物體電生理信號的改變而導致后續(xù)一系列變化如神經遞質紊亂、基因表達改變等。但由于缺乏實時的電磁輻照系統(tǒng),相關研究尚無法開展。因此,基于以上兩方面,建立外加電磁場作用下細胞膜電位計算模型,設計基于細胞電生理記錄的實時電磁輻照裝置對掌握細胞膜電位的變化規(guī)律、開展電磁輻射過程中的生物效應研究及其在生物、醫(yī)學領域的應用具有重要指導意義。且兩部分內容相輔相成,膜電位的理論計算模型研究為預測可能的電磁輻射生物效應提供理論依據(jù);適用于細胞電生理記錄的實時電磁輻照裝置又作為檢測細胞電信號的基礎,為理論計算模型提供驗證手段。綜合以上兩方面的考慮,本文首先建立了外加電磁場作用下,懸液細胞膜電位的理論計算模型,并將模型的適用范圍擴展到高頻電磁場,尤其是頻率高于細胞膜弛豫頻率的情況。隨著頻率的升高,細胞膜的電導率和細胞膜內外的電容特性均需考慮在計算模型中,本文通過有效介質理論和場近似等效的方法將懸液中其他細胞的影響等效于一個局部場的作用,利用已經建立的外電場作用下單個細胞膜電位的計算模型推導出外加高頻電磁場作用下,懸液細胞膜電位的計算模型。計算結果表明:在頻率較低時,懸液細胞膜電位受頻率、細胞濃度、排列方式等因素的影響,而當頻率較高時,頻率上升為主導因素。由于細胞內、外液的介電弛豫效應,跨膜電位沒有隨著頻率升高而單調的下降,而是在中間某個頻段出現(xiàn)了平臺效應,之后隨頻率繼續(xù)上升膜電位再重新下降。最后與其他類似的計算模型(低頻)以及數(shù)值計算結果進行對比,分析了理論計算模型與數(shù)值計算結果存在偏差的原因——有效介質理論和場近似等效的方法不能精確的計算出懸液中局部電勢/場分布。并提出了一種基于Bergman譜理論的可能解決方法。實際上,建立外加電場作用下懸液中細胞膜電位的理論計算模型,其關鍵在于精確的計算出細胞懸液的局部電場或電勢分布,我們將非均質細胞單殼模型等效為均質小球模型后,實質上細胞懸液就轉化成了一個二元復合介質,而基于Bergman譜理論的方法正好可以精確的計算復合介質中的電場和電勢分布。第二部分內容,首先根據(jù)生物實驗的需要,確定電磁輻照裝置的結構為開放式傳輸線結構,并得到傳輸線結構的尺寸約束條件;然后針對阻抗匹配、單模傳播等電磁特性要求,確定電磁輻照裝置的結構為微屏蔽共面波導。利用保角變換法推導了微屏蔽共面波導的結構尺寸與特征阻抗關系的解析式,再結合已有的尺寸約束條件初步確定了微屏蔽共面波導的結構尺寸參數(shù)。通過CST電磁仿真軟件分別建立了無生物樣本和有生物樣本兩種情況下的微屏蔽共面波導電磁仿真模型,得到了無生物樣本模型的S參數(shù)、場分布以及有生物樣本模型的SAR分布及其均勻性等關鍵性參數(shù)。針對細胞懸液中凹液面對SAR分布的影響,又建立了含凹液面的培養(yǎng)皿模型,對比了平液面和凹液面的SAR分布情況,仿真結果顯示凹液面對SAR分布具有明顯影響。針對生物樣本SAR均勻性問題,提出了改變激勵方式的方法——由一端激勵變?yōu)閮啥送瑫r激勵,仿真結果表明生物樣本的SAR的均勻性有較大改善。針對電磁干擾問題,擬采用改變電極插入角度、延長玻璃電極長度等多種方式減少電磁場對電極的干擾。最后,由于MEMS技術加工微屏蔽共面波導的尺寸限制和成本問題,提出了一種新的加工工藝流程,將微屏蔽共面波導分成兩部分,通過PCB加工和機械加工后再組合的方式解決了微屏蔽共面波導的加工制造問題。綜上,電磁仿真結果表明設計方法合理、可靠,設計的未屏蔽共面波導裝置完全符合電磁和生物實驗的兩方面要求,并且各參數(shù)性能較目前已有的照射裝置更好�？紤]到整個照射系統(tǒng)組建、調試和膜片鉗實驗的復雜性,仍需生物實驗驗證,這部分工作將在今后開展。
[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.
【學位授予單位】：中國人民解放軍軍事醫(yī)學科學院
【學位級別】：博士
【學位授予年份】：2015
【分類號】：R594.8

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