Intense but short electrical fields can increase the permeability of the cell membrane in a process referred to as electroporation. Reversible electroporation has become an important tool in biotechnology and medicine. The various applications of reversible electroporation require cells to survive the procedure, and therefore the occurrence of irreversible electroporation (IRE), following which cells die, is obviously undesirable. However, for the past few years, IRE has begun to emerge as an important minimally invasive nonthermal ablation technique in its own right as a method to treat tumors and arrhythmogenic regions in the heart. IRE had been studied primarily to define the upper limit of electrical parameters that induce reversible electroporation. Thus, the delineation of IRE from thermal damage due to Joule heating has not been thoroughly investigated. The goal of this study was to express the upper bound of IRE (onset of thermal damage) theoretically as a function of physical properties and electrical pulse parameters. Electrical pulses were applied to THP-1 human monocyte cells, and the percentage of irreversibly electroporated (dead) cells in the sample was quantified. We also determined the upper bound of IRE (onset of thermal damage) through a theoretical calculation that takes into account the physical properties of the sample and the electric pulse characteristics. Our experimental results were achieved below the theoretical curve for the onset of thermal damage. These results confirm that the region to induce IRE without thermal damage is substantial. We believe that our new theoretical analysis will allow researchers to optimize IRE parameters without inducing deleterious thermal effects.

1.
Zimmermann
,
U.
,
Pilwat
,
G.
,
Beckers
,
F.
, and
Riemann
,
F.
, 1976, “
Effects of External Electrical Fields on Cell Membranes
,”
Bioelectrochem. Bioenerg.
0302-4598,
3
, pp.
58
83
.
2.
Davalos
,
R. V.
,
Mir
,
L. M.
, and
Rubinsky
,
B.
, 2005, “
Tissue Ablation With Irreversible Electroporation
,”
Ann. Biomed. Eng.
0090-6964,
33
(
2
), pp.
223
231
.
3.
Edd
,
J. F.
,
Horowitz
,
L.
,
Davalos
,
R. V.
,
Mir
,
L. M.
, and
Rubinsky
,
B.
, 2006, “
In Vivo Results of a New Focal Tissue Ablation Technique: Irreversible Electroporation
,”
IEEE Trans. Biomed. Eng.
0018-9294,
53
(
7
), pp.
1409
1415
.
4.
Rubinsky
,
B.
,
Onik
,
G.
, and
Mikus
,
P.
, 2007, “
Irreversible Electroporation: A New Ablation Modality—Clinical Implications
,”
Technol. Cancer Res. Treat.
1533-0346,
6
(
1
), pp.
37
48
.
5.
Rubinsky
,
B.
, 2007, “
Irreversible Electroporation in Medicine
,”
Technol. Cancer Res. Treat.
1533-0346,
6
(
4
), pp.
255
260
.
6.
Onik
,
G.
,
Mikus
,
P.
, and
Rubinsky
,
B.
, 2007, “
Irreversible Electroporation: Implications for Prostate Ablation
,”
Technol. Cancer Res. Treat.
1533-0346,
6
(
4
), pp.
295
300
.
7.
Al-Sakere
,
B.
,
Bernat
,
C.
,
Andre
,
F.
,
Connault
,
E.
,
Opolon
,
P.
,
Davalos
,
R. V.
, and
Mir
,
L. M.
, 2007, “
A Study of the Immunological Response to Tumor Ablation With Irreversible Electroporation
,”
Technol. Cancer Res. Treat.
1533-0346,
6
, pp.
301
306
.
8.
Al-Sakere
,
B.
,
Andre
,
F.
,
Bernat
,
C.
,
Connault
,
E.
,
Opolon
,
P.
,
Davalos
,
R. V.
,
Rubinsky
,
B.
, and
Mir
,
L. M.
, 2007, “
Tumor Ablation With Irreversible Electroporation
,”
PLoS ONE
1932-6203,
2
(
11
), p.
e1135
.
9.
Lavee
,
J.
,
Onik
,
G.
,
Mikus
,
P.
, and
Rubinsky
,
B.
, 2007, “
A Novel Nonthermal Energy Source for Surgical Epicardial Atrial Ablation: Irreversible Electroporation
,”
Heart Surg. Forum
,
10
(
2
), pp.
E162
EI67
. 1098-3511
10.
Hoffman
,
G. A.
, 1989, “
Cells in Electric Field. Physical and Practical Electronic Aspects of Electro Cell Fusion and Electroporation
,”
Electroporation and Electrofusion in Cell Biology
,
E.
Neumann
,
A. E.
Sowers
, and
C. A.
Jordan
, eds.,
Plenum
,
New York
, pp.
389
407
.
11.
Kekez
,
M. M.
,
Savic
,
P.
, and
Johnson
,
B. F.
, 1996, “
Contribution to the Biophysics of the Lethal Effects of Electric Field on Microorganisms
,”
Biochim. Biophys. Acta
0006-3002,
1278
(
1
), pp.
79
88
.
12.
Krassowska
,
W.
,
et al.
, 2003, “
Viability of Cancer Cells Exposed to Pulsed Electric Fields: The Role of Pulse Charge
,”
Ann. Biomed. Eng.
0090-6964,
31
(
1
), pp.
80
90
.
13.
Okino
,
M.
,
et al.
, 1992, “
Optimal Electric Conditions in Electrical Impulse Chemotherapy
,”
Jpn. J. Cancer Res.
0910-5050,
83
(
10
), pp.
1095
1101
.
14.
Shoenbach
,
K. H.
,
et al.
, 1997, “
The Effect of Pulsed Fields on Biological Cells: Experiments and Applications
,”
IEEE Trans. Biomed. Eng.
0018-9294,
25
, pp.
284
292
.
15.
Vernhes
,
M. C.
,
Cabanes
,
P. A.
, and
Teissie
,
J.
, 1999, “
Chinese Hamster Ovary Cells Sensitivity to Localized Electrical Stresses
,”
Bioelectrochem. Bioenerg.
0302-4598,
48
(
1
), pp.
17
25
.
16.
Martin
,
G. T.
,
Pliquett
,
U. F.
, and
Weaver
,
J. C.
, 2002, “
Theoretical Analysis of Localized Heating in Human Skin Subjected to High Voltage Pulses
,”
Bioelectrochemistry
1567-5394,
57
(
1
), pp.
55
64
.
17.
Tropea
,
B. I.
, and
Lee
,
R. C.
, 1992, “
Thermal Injury Kinetics in Electrical Trauma
,”
ASME J. Biomech. Eng.
0148-0731,
114
(
2
), pp.
241
250
.
18.
Edd
,
J. F.
, and
Davalos
,
R. V.
, 2007, “
Mathematical Modeling of Irreversible Electroporation for Treatment Planning
,”
Technol. Cancer Res. Treat.
1533-0346,
6
, pp.
275
286
.
19.
Davalos
,
R. V.
, and
Rubinsky
,
B.
, 2008, “
Temperature Considerations During Irreversible Electroporation
,”
Int. J. Heat Mass Transfer
0017-9310,
51
(
23–24
), pp.
5617
5622
.
20.
Ivorra
,
A.
, and
Rubinsky
,
B.
, 2007, “
Electric Field Modulation in Tissue Electroporation With Electrolytic and Non-Electrolytic Additives
,”
Bioelectrochemistry
1567-5394,
70
(
2
), pp.
551
560
.
21.
Ivorra
,
A.
, and
Rubinsky
,
B.
, 2007, “
In Vivo Electrical Impedance Measurements During and After Electroporation of Rat Liver
,”
Bioelectrochemistry
1567-5394,
70
(
2
), pp.
287
295
.
22.
Davalos
,
R. V.
,
Rubinsky
,
B.
, and
Mir
,
L. M.
, 2003, “
Theoretical Analysis of the Thermal Effects During In Vivo Tissue Electroporation
,”
Bioelectrochemistry
1567-5394,
61
(
1–2
), pp.
99
107
.
23.
Miller
,
L.
,
Leor
,
J.
, and
Rubinsky
,
B.
, 2005, “
Cancer Cells Ablation With Irreversible Electroporation
,”
Technol. Cancer Res. Treat.
1533-0346,
4
(
6
), pp.
699
705
.
24.
White
,
F. M.
, 1991,
Heat and Mass Transfer
,
Addison-Wesley
,
Reading, MA
, p.
718
.
25.
Feng
,
Y.
,
Tinsley Oden
,
J.
, and
Rylander
,
M. N.
, 2008, “
A Two-State Cell Damage Model Under Hyperthermic Conditions: Theory and In Vitro Experiments
,”
ASME J. Biomech. Eng.
0148-0731,
130
(
4
), p.
041016
.
26.
Schneider
,
P. J.
, 1955,
Conduction Heat Transfer
,
Addison-Wesley
,
Reading, MA
.
27.
Weaver
,
J. C.
, and
Chizmadzhev
,
Y. A.
, 1996, “
Theory of Electroporation: A Review
,”
Bioelectrochem. Bioenerg.
0302-4598,
41
(
2
), pp.
135
160
.
28.
Krassowska
,
W.
, and
Filev
,
P. D.
, 2007, “
Modeling Electroporation in a Single Cell
,”
Biophys. J.
0006-3495,
92
(
2
), pp.
404
417
.
29.
Heisler
,
M. P.
, 1947, “
Temperature Charts for Induction and Constant Temperature Heating
,”
Trans. ASME
0097-6822,
69
, pp.
227
236
.
30.
Henriques
,
F. C.
, and
Moritz
,
A. R.
, 1947, “
Studies in Thermal Injuries, V: The Predictability and the Significance of Thermally Induced Rate Processes Leading to Irreversible Epidermal Damage
,”
Arch. Pathol.
0363-0153,
43
, pp.
489
502
.
31.
Diller
,
K. R.
, and
Hayes
,
L. J.
, 1983, “
A Finite Element Model of Burn Injury in Blood-Perfused Skin
,”
ASME J. Biomech. Eng.
0148-0731,
105
(
3
), pp.
300
307
.
32.
Jiang
,
S. C.
,
Ma
,
N.
,
Li
,
H. J.
, and
Zhang
,
X. X.
, 2002, “
Effects of Thermal Properties and Geometrical Dimensions on Skin Burn Injuries
,”
Burns
0305-4179,
28
(
8
), pp.
713
717
.
33.
Weaver
,
J. C.
, and
Powell
,
K. T.
, 1989, “
Theory of Electroporation
,”
Electroporation and Electrofusion in Cell Biology
,
E.
Neumann
, ed.,
Plenum
,
New York
.
34.
Mir
,
L. M.
, and
Orlowski
,
S.
, 1999, “
Mechanisms of Electrochemotherapy
,”
Adv. Drug Delivery Rev.
0169-409X,
35
, pp.
107
118
.
You do not currently have access to this content.