生物医用冲激脉冲辐射聚焦天线研究
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摘要
目前,传统癌症治疗方法如手术治疗、放射治疗和化学药物治疗等,其机理在于杀伤并抑制肿瘤细胞的生长与增殖,因而只能延缓肿瘤的进展,不能达到治愈的目的。而微/纳秒电场脉冲治疗肿瘤方法需要采用有创/微创电极或电极阵列以穿刺的方式才能引导至肿瘤组织,这都会对患者的生理和心理将产生严重的负面影响。寻找一种既能够有效杀灭肿瘤细胞、同时又能提高患者生存质量的肿瘤无创治疗手段,一直是医患双方的期盼。
高强度电场脉冲的脉宽从纳秒级进入到亚纳秒级甚至皮秒级,将使得电场脉冲对生物体结构和功能的影响研究进入新的领域。整合无创治疗的应用需求以及电场脉冲靶向诱导肿瘤细胞凋亡的窗口效应,本文提出通过冲激脉冲辐射天线将皮秒脉冲聚焦于肿瘤组织,使肿瘤细胞线粒体跨膜电位发生变化而崩溃,启动线粒体途径的凋亡靶向诱导,实现肿瘤的无创治疗。
由于皮秒电场脉冲匹配超宽带时域天线技术具有优异的方向性和精细的操控性,本文根据超宽带天线设计理论,首次设计出了一种用于辐射皮秒电场脉冲的冲激脉冲辐射聚焦天线。初步优化结果显示当金属板与x-轴夹角β为90°~95°以及单圆锥辐射器的半张角θ为30°~35°时,可以使天线在靶点位置得到最大的电场分布,并通过口径场法分析了靶点位置的场强;天线在焦点区域的电场分布保持了输入脉冲的冲激特性,电压驻波比小于2,且具有稳定的增益和场方向图,x-轴方向电场分布的半峰带宽小于20mm,y-轴和z-轴方向小于10mm,具有很高的时间分辨率和空间分辨率;同时,考虑介质透镜聚焦理论的引入,在靶点位置放置介质透镜,可以使电场脉冲在耦合介质之间无衰减或尽量少衰减的传播,从而在靶点位置可以得到更高的场强分布。
At present, the traditional cancer treatments such as surgery, radiation therapy and chemotherapy treatment, the mechanism of which are to damage or inhibit the growth and proliferation of tumor cells, can only delay the progression without achieving the purpose of cure. The method with micro / nanosecond electric pulses requires the treatment of cancer using invasive / minimally invasive needle electrode or electrode array in a way as to lead to the tumor tissue, which may have serious negative effects on the patient's physical and mental will. To find an effective way to kill tumor cells and improve the quality of life of cancer patients with non-invasive treatment has been the expectations of both doctors and patients.
By reducing the pulse width of high intensity electric field from nanosecond to sub-nanosecond or picoseconds level,it will lead the research of pulses on the structure and function of organisms to a new field. Considering the application of non-invasive treatment and window effects of cell apoptosis targeted induced by electric pulses,method of non-invasive treatment of tumors was proposed in this research. With picosecond pulse being focused on the tumor tissue by using Impulse Radiating Antenna(IRA),the mitochondrial transmembrane would change to collapse under which the tumor cells could be targeted induced to apoptosis in mitochondrial pathway.
Picosecond electric pulses with the time-domain ultra-wideband antenna technology have excellent directivity and fine maneuverability. Based on the theory ultra-wide-band antenna,we designed an Impulse Radiating Antenna by which picosecond pulses can be radiated and some preliminary optimizations of the antenna were made. Whileβwas 90°~95°andθwas 30°~35°,the maximum E-field distribution could be achieved and the analytical field strength of target location can be got with the aperture-field analysis. At the same time, the gain and field pattern of the antenna are stable, and the voltage standing wave ratio is less than 2. And the pulse of focusing region maintains the input impulse characteristics, while the full width at high maximum of the E-field distribution generated in x-axis direction is less than 20mm, with y-axis and z-axis 10mm.The antenna is designed with high time resolution and spatial resolution. Considering the introduction of the theory of dielectric lens focused in the target location where to place dielectric lens, which can make the electric pulses spread in coupling medium in a non-attenuated way, with as little as possible decay, so a higher E-field intensity distribution can be achieved in target position.
高强度电场脉冲的脉宽从纳秒级进入到亚纳秒级甚至皮秒级,将使得电场脉冲对生物体结构和功能的影响研究进入新的领域。整合无创治疗的应用需求以及电场脉冲靶向诱导肿瘤细胞凋亡的窗口效应,本文提出通过冲激脉冲辐射天线将皮秒脉冲聚焦于肿瘤组织,使肿瘤细胞线粒体跨膜电位发生变化而崩溃,启动线粒体途径的凋亡靶向诱导,实现肿瘤的无创治疗。
由于皮秒电场脉冲匹配超宽带时域天线技术具有优异的方向性和精细的操控性,本文根据超宽带天线设计理论,首次设计出了一种用于辐射皮秒电场脉冲的冲激脉冲辐射聚焦天线。初步优化结果显示当金属板与x-轴夹角β为90°~95°以及单圆锥辐射器的半张角θ为30°~35°时,可以使天线在靶点位置得到最大的电场分布,并通过口径场法分析了靶点位置的场强;天线在焦点区域的电场分布保持了输入脉冲的冲激特性,电压驻波比小于2,且具有稳定的增益和场方向图,x-轴方向电场分布的半峰带宽小于20mm,y-轴和z-轴方向小于10mm,具有很高的时间分辨率和空间分辨率;同时,考虑介质透镜聚焦理论的引入,在靶点位置放置介质透镜,可以使电场脉冲在耦合介质之间无衰减或尽量少衰减的传播,从而在靶点位置可以得到更高的场强分布。
At present, the traditional cancer treatments such as surgery, radiation therapy and chemotherapy treatment, the mechanism of which are to damage or inhibit the growth and proliferation of tumor cells, can only delay the progression without achieving the purpose of cure. The method with micro / nanosecond electric pulses requires the treatment of cancer using invasive / minimally invasive needle electrode or electrode array in a way as to lead to the tumor tissue, which may have serious negative effects on the patient's physical and mental will. To find an effective way to kill tumor cells and improve the quality of life of cancer patients with non-invasive treatment has been the expectations of both doctors and patients.
By reducing the pulse width of high intensity electric field from nanosecond to sub-nanosecond or picoseconds level,it will lead the research of pulses on the structure and function of organisms to a new field. Considering the application of non-invasive treatment and window effects of cell apoptosis targeted induced by electric pulses,method of non-invasive treatment of tumors was proposed in this research. With picosecond pulse being focused on the tumor tissue by using Impulse Radiating Antenna(IRA),the mitochondrial transmembrane would change to collapse under which the tumor cells could be targeted induced to apoptosis in mitochondrial pathway.
Picosecond electric pulses with the time-domain ultra-wideband antenna technology have excellent directivity and fine maneuverability. Based on the theory ultra-wide-band antenna,we designed an Impulse Radiating Antenna by which picosecond pulses can be radiated and some preliminary optimizations of the antenna were made. Whileβwas 90°~95°andθwas 30°~35°,the maximum E-field distribution could be achieved and the analytical field strength of target location can be got with the aperture-field analysis. At the same time, the gain and field pattern of the antenna are stable, and the voltage standing wave ratio is less than 2. And the pulse of focusing region maintains the input impulse characteristics, while the full width at high maximum of the E-field distribution generated in x-axis direction is less than 20mm, with y-axis and z-axis 10mm.The antenna is designed with high time resolution and spatial resolution. Considering the introduction of the theory of dielectric lens focused in the target location where to place dielectric lens, which can make the electric pulses spread in coupling medium in a non-attenuated way, with as little as possible decay, so a higher E-field intensity distribution can be achieved in target position.
引文
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[3]姚陈果,孙才新,米彦等.陡脉冲不可逆性电击穿治疗肿瘤的研究[J].高电压技术, 2007, 33(2): 7-13.
[4] Schoenbach KH, Xiao S, Joshi RP, et al. The Effect of Intense Subnanosecond Electrical Pulses on Biological Cells[J]. IEEE Transactions on Dielectrics and Electrical Insulation, 2008, 36(2):414-422.
[5] Baum CE, Farr EG. Ultra-Wideband, Short-Pulse Electromagnetics[M]. Springer Press. 1993.
[6] Schoenbach KH, Joshi RP. Ultrashort Electrical Pulses Open a New Gateway into Biological Cells[C]. Proceedings of the IEEE, 2004, 92(7): 1122-1137.
[7] Schoenbach KH, Nuccitelli R, Beebe SJ. Zap[J]. IEEE Spectrum, 2006, 43(8): 20-28.
[8] Schantz H. A Brief History of UWB Antennas[J]. IEEE on Aerospace and Electronic Systems Magazine, 2004, 19(5):22-26.
[9]唐军.超宽带无线技术-UWB[J].现代通信, 2003, 20(3):17-19.
[10]杨晓非,刘银碧,代睿. UWB技术及前景探讨[J].数据通信, 2003, 14(5):12-14.
[11] FCC News Release, New Public Safety Applications and Broadband Internet Access among Uses Envisioned by FCC Authorization of Ultra-Wideband Technology. 2002, 2.
[12] FCC 02-48, Revision of Part 15 of the Commission’s Rules Regarding Ultra-Wideband Transmission Systems. First Report & Order, Washington DC, 2002, 2.
[13] Yarovoy AG, Ligthart LP, Ultra-wideband technology today[M]. Warszawa, Poland, 2004.
[14] Xuan HW. Note on Antenna Design in UWB Wireless Communication Systems[C]. IEEE Conference on UltraWideband Systems and Technologies, 2003:503-507.
[15] Stutzman WL, Thiele GA, Antenna Theory and Design [M], John Wiley & Sons, 1998.
[16] Taylor JD, Introduce to Ultra-Wideband Radar Systems[M], CRC Press Inc, 1995.
[17]李甲子.超宽带天线及信道的等效电路建模研究[D],浙江:浙江大学,2008.
[18]李长勇,杨士中,张承畅等.超宽带脉冲天线研究综述[J].电波科学学报. 2008:28(5):1003-1008.
[19] Adrian N. Ground-penetrating radar and its use in sedimentology: principles, problems and progress [J]. Earth-Science Reviews, 2004, 66:261-330.
[20]陈义群,肖柏勋.论探地雷达现状与发展[J].工程地球物理学报, 2005, 2(2):149-155.
[21] David L, Leon S. Baseband-Pulse-Antenna Techniques [J]. IEEE Antennas and Propagation Magazine, 1994, 36(1):20-30.
[22] Oliver E Allen, David A. Hill.Time-Domain Antenna Characterizations [J].IEEE Transactions on Electromagnetic Compatibility, 1993, 35(3):339-346.
[23] Wang N, Xue ZH, Yang SM. Antenna Time Domain Planar Near Field Measurement System[J]. International Journal on Wireless and Optical Communications, 2006, 3(2):127-133.
[24]沈捷.基于超宽带应用的天线等效电路模型[D].浙江:浙江大学, 2006.
[25]张安荣.小型化宽频带平面单极天线的设计[D].北京:北京交通大学, 2007.
[26]刘小龙.超宽带高功率脉冲天线研究[D].西安:西安交通大学, 2003.
[27]孟凡宝,杨周炳,吴文涛等.高功率超宽带同轴双锥天线的设计和实验[J].强激光与粒子束, 1999, 11(2):245-247.
[28] Neumann E, Rosenheck K. Permeability changes induced by electric impulses in vesicular membranes[J]. Journal of Membrane Biology, 1972, 10:279-290.
[29] Crowley JM. Electrical breakdown of biomolecular lipid membranes as an electromechanical instability[J]. Biophysical Journal, 1973, 13: 711-724.
[30] Zimmermann U, Friedrich U, Mussauer H, et al. Electromanipulation of Mammalian Cells: Fundamentals and Application[J]. IEEE Trans on Plasma Science, 2000, 28(1): 72-82.
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