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Electric Field Effects on Tumor cell
Document By SANTOSH BHARADWAJ REDDY Email: email@example.com
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Abstract- High voltage engineering has wide applications.. This study is one of the application of high voltage engineering in medical field. Exposing tumor cells to pulsed electric field causes built up of charges in the cell membrane and may result in the dielectric breakdown of the membrane. PEF of several kilovolts per centimeter amplitude and sub microsecond duration have been found to prevent the growth of tumor cell. Electric field effect of tumor cell is studied for different electrode configuration using finite element method. Different electrodes used are plate and needle electrode.
IndexTerms— tumor cell, pulsed electric field, plate and needle electrodes, finite element method.
believed that the pore formation generates large openings in membrane accounting for transfer of large molecules across the tumor cell membrane. Eleectoporation is a critical parameter involved in the treatment of cancer. Under normal physiological condition the cell membrane conductance is several orders of magnitude lower than that of external medium. When high voltage is applied electroporation occurs. Due to electroporation there will be an increase in conductance value and result in the rupture of the cell wall.(fig 1)
INTRODUCTION Pulsed electric fields are known to have been used for many applications. Some of them are Befouling Prevention, Medical Applications and Bacterial Decontamination. The most advanced medical application is used for cancer treatment . Here the tumor cell is treated with pulsed electric field of 10-100 microsecond duration and amplitude of the order of 10kV/cm. This is done by means of electrode array inserted in to the affected tissue. So it is necessary to study about the electric field distribution of different electrode configuration. In this study, the electrode configurations considered are plate electrode and needle electrode where plate electrode is used to study the electrical field distribution of uniform field and needle electrode is used to study about the electrical field distribution of nonuniform field Cells exposed to short and intense electric pulses become permeable to number of various ionic molecules. This phenomenon is termed electroporation. Tissues can also be permeabilised. These approach based on electroporation are used for cancer treatment. The use of high voltage pulse power is used to prevent the growth of tumor cell. Thus an attempt has been made to study the electrical field effect on tumor cells. Exposing tumor cells to pulsed electric field causes build up of charges in the cell membrane and consequently a change in the transmembrane potential of the cell. For low electric fields, this causes voltage gating of the protein channels in the cell membrane. With increasing electric field induced transmembrane voltages on the order of 1V forms electropores on tumour cell membrane . It is
Fig 1 dielectric breakdown of cell membrane III. ELECTROPORATION THERAPY Electroporation (EP) explained as a phenomenon in which a cell exposed to the high voltage electric field that temporarily destabilizes the Bilayer Lipid Membrane (BLM) and protein channels of the cell membrane. The opening and closing of closing channel is dependent on TMP. The gating potential of the channels constituted by proteins is in the range 50mV. When PEF is applied, the voltage sensitive protein channels will open, experience current much larger that the current normally experienced during metabolic activities and as a result of protein channels are irreversibly denatured (i.e. eliminates enzyme activities of the protein
2 channels). The lipid bilayer is also susceptible to applied electric fields due to its net electric charge. The application of electric field causes lipid molecules to reorient thus creating hydrophilic pores which conduct current and eventually leads to the rupture of cell wall. Thus electroporation in the tumor cell membrane occurs both in protein channels and in the lipid bilayers resulting in the inactivation of tumor cell. both the side of the tumor cell. High voltage of the order of 20kV is been applied and electric field distribution is studied for plate and needle electrode. The electrode gap spacing is about 10mm. The tumor cell is placed in low conductivity medium. Mostly the cell membrane thickness is small compared to the size of the cell.
FIG(3) CELL MODEL
VI. PARAMETERS USED IN SIMULATION Table 1: Tumor cell parameters A. Parameters Cytoplasm conductivity Cytoplasmic permittivity Membrane conductivity Membrane permittivity Extracellular medium conductivity Cell radius Membrane thickness Distance between the electrodes I. DENOTATION AND VALUE 0.48 S/m 60 As/Vm 9.1e-6S/m 9.8 As/Vm 1e-2S/m 10µ m 5nm 10mm
Fig 2. Electroporation of cell membrane
IV. PEF IN CANCER TREATMENT Some of the methods used for treating cancer are surgery, chemotherapy, radiation therapy, immunotherapy, monoclonal antibody therapy etc. Choice of therapy depends upon loction and grade of tumor and stage of disease and state of patient. Surgery and radiation therapies are the major curative modalities. Use of chemotherapy along with short electrical pulses could be more effective for treatment of cancer. Complete removal of cancer cell without damage to the rest of the body is the goal of treatment. Sometimes this can be accomplished by Surgery but the propensity of cancer to invade adjacent tissue or to spread to distant sites by microscopic metastatis often limits its effectiveness. Effectiveness of chemotherapy is limited by toxicity to other tissues in the body. Radiation can also cause damage to normal tissues. . There are many potential advantages of electroporation therapy over conventional treatments. It may be best suitable for cancers near critical organs where surgery and/or radiation therapy have failed. Furthermore, this treatment modality has the potential of overcoming the multidrug resistance problem and it has been reported to reduce the number of metastatic nodules when primary tumor was treated. PEF can be performed at relatively low, non-toxic drug concentration as a single treatment with minimal side effects; it may be suitable for nonresectable tumors and can save functional tissues. This is the reason for moving to pulsed electric field method for treating cancer. V.TUMOR CELL MODEL The following tumour cell model is used in the ANSOFT analysis. The tumor cell has its own parameters which is given in table (5). Two electrodes are placed on
VII ELECTRIC FIELD DISTRIBUTION FOR TUMOR CELL A.PLATE ELECTRODE The field distribution for plate electrode is shown below. Plate electrode is used to show the uniformity of the field. Uniformity in the sense that the electric field distribution for the plate electrode is uniform. Here since plate electrode is considered, the stress is uniform. Further electric field strength required is high for this type of electrode.
3 field i.e electric field distribution is not uniform here. Stress is more since non-uniform electrode is used. In this configuration electric field intensity is less compared to that of plate electrode. (a)
(c) plot Fig 4 (a). equipotential plot for tumor cell (b) phi (c) stress plot
From the figure 4(b) it is observed at high voltage surface , the potential is maximum and it goes on decreasing when the distance between electrode increases. Similarly from fig 4(c), the electric field intensity is high at the high voltage electrode surface. B. NEEDLE ELECTRODE
The field distribution for needle electrode is shown below. Needle electrode is used to show the non- uniformity of the
4 (d) Fig (a) equipotential plot for needle electrode (b) phi(lineline ) for needle electrode (c) stress plot (d) magnitude E plot From fig 5(c) it is observed that for non uniform field, at the high voltage surface potential is maximum and it goes on decreasing when distance between electrode increases. VIII. RESULTS AND DISCUSSIONS Finite element method is used to simulate the electric field generated by different electrode configuration in a cancer cell. Generally electric field of the order of 1050kV is needed to kill the tumour cells. Here electric field analysis was carried out for plate and needle electrode configuration and the field intensity was calculated numerically. From the stress plot it can be concluded that , non invasive plate electrodes are better suited for tumors on the surface of the skin, whereas needle electrodes are used with appropriate depth of insertion, more suitable for treating subcutaneous tumor seeded deeper in the skin. For a given electrode size and spacing between the electrodes, electrode shape has no influence on electric field because of uniformity of the field. But the needle shaped electrode has influence of electric field due to non uniformity in the field II. CONCLUSION Finite Element Analysis investigates the electric field intensity as a function of distance under uniform and non-uniform field. From this study it is seen that plate electrode have high electric field intensity whereas it is less for needle electrode. Since needle electrode have nonuniform field, it breaksdown earlier. So it needs less electric field intensity. transations on biomedical engineering, vol 53, no 5, june 2006. (page 1409-1415) TCRT(Technology I cancer research),”Towards Solid Tumor Treatment by Irrerversible Electroporation: Intrinsic Redistribution of Fields and currents in Tissue”, August 2007(page 261-274) S.B Dev, G.S. Nanda and Z.an, "Enhancement of Bleomycin Cytotoxicity to tumor cells by Pulsed Electric Field", IEEE Engineering in Medicine and Biology Society, 1996.(page 1877-1878) Eilon D. Kirson, Zoya Gurvich, Rosa Schneiderman, Erez Dekel,"Disruption of cancer cell replication by alternating electric fields,", cancer research,may 2004.(page 3288-3295) Meny, N. Burais, F. Buret and L. Nicolas,"Finite Element Modelling of Cell Exposed to Harmonic and Transient Electric Fields", IEEE transactions on magnetics, vol 43, no 4, april 2007 Karl H. Schoenbach, Barbara Hargrave, Ravindra P. Joshi, Juergen F. Kolb,"Bioelectric Effects of Intense Nanosecond Pulses" IEEE transactions on dielectrics and electrical insulation, july 2007 (page 10881104). Olivier clatz, Maxime Sermesant, Pierre-Yves bondiau, simon K warfield,"Realistic Simulation of the 3-D Growth of Brain tumors in MR Images Coupling Diffusion With Biomechanical Deformation", IEEE transactions on medical imaging, vol 24, no10, oct 2005 D.Sorden, J.Larkin, C.Collins, J.Piggot,"The Development of Novel Flexible Electrode Arrays for the Electrochemotherapy of Solid Tumor Tissue", proceedings of the 26th Annual International Conference of the IEEE EMBS, Sep 2004.(page 3547-3550)
Corresponding Author: A.Priyadharsini,Department of Electrical & Electronics Engineering, College of Engineering, Guindy, Anna University, Chennai25 firstname.lastname@example.org, email@example.com.
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