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Electric Field Effects on Tumor cell


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SANTOSH BHARADWAJ REDDY
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believed that the pore formation generates large openings
Abstract- High voltage engineering has wide in membrane accounting for transfer of large molecules
applications.. This study is one of the application of high across the tumor cell membrane. Eleectoporation is a
voltage engineering in medical field. Exposing tumor cells critical parameter involved in the treatment of cancer.
to pulsed electric field causes built up of charges in the Under normal physiological condition the cell membrane
cell membrane and may result in the dielectric conductance is several orders of magnitude lower than that
breakdown of the membrane. PEF of several kilovolts per of external medium. When high voltage is applied
centimeter amplitude and sub microsecond duration have
electroporation occurs. Due to electroporation there will be
been found to prevent the growth of tumor cell. Electric
an increase in conductance value and result in the rupture
field effect of tumor cell is studied for different electrode
configuration using finite element method. Different of the cell wall.(fig 1)
electrodes used are plate and needle electrode.

IndexTerms— tumor cell, pulsed electric field, plate and


needle electrodes, finite element method.

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 [1]. 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[4]. 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 non-
uniform 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 Fig 1 dielectric breakdown of cell membrane
be permeabilised. These approach based on electroporation
are used for cancer treatment. The use of high voltage pulse III. ELECTROPORATION THERAPY
power is used to prevent the growth of tumor cell. Thus an Electroporation (EP) explained as a phenomenon
attempt has been made to study the electrical field effect on in which a cell exposed to the high voltage electric field that
tumor cells. temporarily destabilizes the Bilayer Lipid Membrane (BLM)
Exposing tumor cells to pulsed electric field causes and protein channels of the cell membrane[7]. The opening
build up of charges in the cell membrane and consequently and closing of closing channel is dependent on TMP. The
a change in the transmembrane potential of the cell. For gating potential of the channels constituted by proteins is in
low electric fields, this causes voltage gating of the protein the range 50mV. When PEF is applied, the voltage sensitive
channels in the cell membrane. With increasing electric protein channels will open, experience current much larger
field induced transmembrane voltages on the order of 1V that the current normally experienced during metabolic
forms electropores on tumour cell membrane [9]. It is 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 both the side of the tumor cell. High voltage of the order of
electric fields due to its net electric charge. The application 20kV is been applied and electric field distribution is studied
of electric field causes lipid molecules to reorient thus for plate and needle electrode. The electrode gap spacing is
creating hydrophilic pores which conduct current and about 10mm. The tumor cell is placed in low conductivity
eventually leads to the rupture of cell wall. Thus medium. Mostly the cell membrane thickness is small
electroporation in the tumor cell membrane occurs both in compared to the size of the cell.
protein channels and in the lipid bilayers resulting in the
inactivation of tumor cell.

FIG(3) CELL MODEL

FIG 3. CELL MODEL

VI. PARAMETERS USED IN SIMULATION


Table 1: Tumor cell parameters

A. Parameters
Fig 2. Electroporation of cell membrane I. DENOTATION AND VALUE
Cytoplasm 0.48 S/m
IV. PEF IN CANCER TREATMENT conductivity
Some of the methods used for treating cancer are surgery, Cytoplasmic 60 As/Vm
chemotherapy, radiation therapy, immunotherapy, permittivity
monoclonal antibody therapy etc. Choice of therapy depends Membrane 9.1e-6S/m
upon loction and grade of tumor and stage of disease and conductivity
state of patient[12]. Surgery and radiation therapies are the Membrane permittivity 9.8 As/Vm
major curative modalities. Use of chemotherapy along with Extracellular medium 1e-2S/m
short electrical pulses could be more effective for treatment conductivity
of cancer. Complete removal of cancer cell without damage Cell radius 10µ m
to the rest of the body is the goal of treatment. Sometimes Membrane thickness 5nm
this can be accomplished by Surgery but the propensity of Distance between the 10mm
cancer to invade adjacent tissue or to spread to distant sites electrodes
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
VII ELECTRIC FIELD DISTRIBUTION FOR TUMOR
normal tissues.
CELL
. There are many potential advantages of
electroporation therapy over conventional treatments. It may
be best suitable for cancers near critical organs where surgery A.PLATE ELECTRODE
and/or radiation therapy have failed. Furthermore, this The field distribution for plate electrode is
treatment modality has the potential of overcoming the shown below. Plate electrode is used to show the uniformity
multidrug resistance problem and it has been reported to of the field. Uniformity in the sense that the electric field
reduce the number of metastatic nodules when primary tumor distribution for the plate electrode is uniform. Here since
was treated[8]. plate electrode is considered, the stress is uniform. Further
PEF can be performed at relatively low, non-toxic electric field strength required is high for this type of
drug concentration as a single treatment with minimal side electrode.
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
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)

(a)

(b)

(b)

(c)

(c)

Fig 4 (a). equipotential plot for tumor cell (b) phi


plot (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) transations on biomedical engineering, vol 53, no 5,


Fig (a) equipotential plot for needle electrode (b) phi(line- june 2006. (page 1409-1415)
line ) for needle electrode (c) stress plot (d) magnitude E [5] TCRT(Technology I cancer research),”Towards Solid
plot Tumor Treatment by Irrerversible Electroporation:
Intrinsic Redistribution of Fields and currents in
From fig 5(c) it is observed that for non uniform Tissue”, August 2007(page 261-274)
field, at the high voltage surface potential is maximum and it [6] S.B Dev, G.S. Nanda and Z.an, "Enhancement of
goes on decreasing when distance between electrode Bleomycin Cytotoxicity to tumor cells by Pulsed
increases. Electric Field", IEEE Engineering in Medicine and
Biology Society, 1996.(page 1877-1878)
VIII. RESULTS AND DISCUSSIONS [7] Eilon D. Kirson, Zoya Gurvich, Rosa Schneiderman,
Erez Dekel,"Disruption of cancer cell replication by
alternating electric fields,", cancer research,may
Finite element method is used to simulate the 2004.(page 3288-3295)
electric field generated by different electrode configuration [8] Meny, N. Burais, F. Buret and L. Nicolas,"Finite
in a cancer cell. Generally electric field of the order of 10- Element Modelling of Cell Exposed to Harmonic and
50kV is needed to kill the tumour cells. Here electric field Transient Electric Fields", IEEE transactions on
analysis was carried out for plate and needle electrode magnetics, vol 43, no 4, april 2007
configuration and the field intensity was calculated [9] Karl H. Schoenbach, Barbara Hargrave, Ravindra P.
numerically. Joshi, Juergen F. Kolb,"Bioelectric Effects of Intense
From the stress plot it can be concluded that , non Nanosecond Pulses" IEEE transactions on dielectrics
invasive plate electrodes are better suited for tumors on the and electrical insulation, july 2007 (page 1088-
surface of the skin, whereas needle electrodes are used with 1104).
appropriate depth of insertion, more suitable for treating [10] Olivier clatz, Maxime Sermesant, Pierre-Yves
subcutaneous tumor seeded deeper in the skin. bondiau, simon K warfield,"Realistic Simulation of
For a given electrode size and spacing between the the 3-D Growth of Brain tumors in MR Images
electrodes, electrode shape has no influence on electric field Coupling Diffusion With Biomechanical
because of uniformity of the field. But the needle shaped Deformation", IEEE transactions on medical imaging,
electrode has influence of electric field due to non uniformity vol 24, no10, oct 2005
in the field [11] D.Sorden, J.Larkin, C.Collins, J.Piggot,"The
Development of Novel Flexible Electrode Arrays for
II. CONCLUSION the Electrochemotherapy of Solid Tumor Tissue",
Finite Element Analysis investigates the electric proceedings of the 26th Annual International
field intensity as a function of distance under uniform and Conference of the IEEE EMBS, Sep 2004.(page
non-uniform field. From this study it is seen that plate 3547-3550)
electrode have high electric field intensity whereas it is less
for needle electrode. Since needle electrode have non- Corresponding Author: A.Priyadharsini,Department of Electrical
& Electronics Engineering, College of Engineering, Guindy, Anna
uniform field, it breaksdown earlier. So it needs less electric University, Chennai25
field intensity. dharshinigce@yahoo.co.in, vg_sree@annauniv.edu.

REFERENCES
[1] .Sukhendu b. dev, Dietmar P. Rabussay, Georg
widera, and Gunter A. Hofmann,”Medical Aplications
of Electroporation”, IEEE transations on plasma
science, vol28, no1, February 2000.
[2] Davora Sel, David cukjati, Danute Batiuskaite,
Tomaz slivnik, “Sequential Finite Element model of
Electropermeabilization”, IEEE transactions on
biomedical engineering, vol 52, no5, may 2005
[3] Damijan Miklavcic, Selma corovic, Gorazd pucihar,
Natasa pavselj, “Importance of Tumour Coverage by
sufficiently high local electric field for effective
chemotherapy”, sciencedirect august 2006.
[4] John F. Edd, Liana Horowitz, ravel V. Davalos,”In
Vivo Results of a New Focal Tissue Ablation
Technique: Irreversible Electroporation”, IEEE

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