314 Bertacchini et al.
Technology in Cancer Research & Treatment, Volume 6, Number 4, August 2007
applied electric eld to kill the cancer cells. However, to
obtain irreversible electroporation of the target tissue, high
voltage pulses need to be generated, the electric eld is
applied by means of electrodes inserted in the tissue to be
treated. Since the amplitude and the gradient of the eld
depend on the applied voltage as well as on the distance be-
tween the electrodes, high values of the electric eld can
be also achieved by arranging the electrodes closer to each
other. However, when treating deep seeded tumors, we de-
sire to introduce the electrodes through the skin both to min-
imize the procedure’s impact and avoid open surgery; thus,
introducing a large number of closely arranged electrodes
to effectively porate the target tissue is not feasible. In this
scenario the goal is to treat a volume of approximately 50
to 70 cm
with up to six electrodes. This requires applied
voltages in the order of 3000 V to obtain irreversible elec-
troporation. The specications of the device ensure that the
electrical eld gradient in a volume 40 cm
is at least 800
V/cm, this is considered to be the threshold for irreversible
electroporation in most cells (13). The electrodes used with
the device are 15 cm long stainless steel needles, partially
insulated, with a diameter of 1 mm. The conductive, non
insulated, distal end of the electrodes can be up to 4 cm long.
The electrodes are inserted under ultrasound guidance.
The high voltages and currents (up to 50 A) used represent
the main problems to be taken into account when designing
a device for irreversible electroporation. Safety issues arise
because of the high energy involved and because of the vari-
able working conditions present in the operating theatre. In
fact, the delivered current depends on the ohmic character-
istics of the tissue under treatment and can differ from point
to point, particularly in the typical heterogeneous tissue that
constitutes tumors. Moreover, the tissue can have its electric
characteristics altered during the treatment, as a consequence
of the deep modications caused to the cells and the extra
cellular environment when high currents are applied.
Consequently in the design of an irreversible electroporator,
one has to keep under control the patient leakage current, to
design a sturdy and fast high voltage pulse generator, with an
high reactivity in case of failure and provide a user-friendly in-
terface for the operators to minimize the chance of user error.
This paper describes the solutions adopted to solve all these
challenging issues in the design and implementation of a
device for irreversible electroporation to be used in the
General Safety Remarks
In addition to general safety requirements for medical de-
vices stated by regulation and standards (14, 15, 16), specic
safety issues characterize electroporation devices. The prin-
cipal hazards derive from the high energy that is accumulated
on capacitors and from the delivery of high electrical current
to the patient, which involves the risk of electrocution for
both the patient and the operator.
Energy release to the patient must be reliably controlled and
limited: unintended or incorrect release has to be avoided.
Strictly related to this issue is device ruggedness: in the
absence of adequate protective measures, a failure of some
critical component may lead to a complete, unwanted dis-
charge of the accumulated energy.
Reliable energy delivery control characterize the normal de-
vice operation and can be ensured by specic safety mea-
sures implemented in the software/rmware. This goal is
achieved by carrying out risk analysis in the earliest phases
of the device architecture design, in order to identify those
hardware parts that must support software safety features;
ensuring that critical device control is carried out by reliable
programmable systems, and implementing best software/
rmware development practices (17).
Energy delivery limitation refers to fault conditions. It is a
strategic choice: risk control may be obtained either by limit-
ing the probability of a failure, in particular for those critical
components whose failure may lead to uncontrolled energy
delivery to the patient, or by implementing an independent
system that prevents energy delivery above the maximum
normal-condition value; both solutions have pros and cons.
In any case the system must be sufciently rugged to conne
such failure to a remotely likely event.
Ruggedness is intended in particular against short circuits
and sparks that are likely to occur between electrodes due to
the unpredictability of the resistive load of biological tissues,
the presence of conductive solutions and human error.
The likelihood of an electroporation treatment to lead to
electrocution depends on several factors: the applied pulse
voltage, the length of the pulses, the number of pulses, the
pulse repetition rate and, of course, the distance between
the hearth and the electrodes (18). Generally speaking,
synchronization of treatment delivery with the refractory
period of the cardiac cycle is always advisable when there
is not enough condence that the electroporation treatment
cannot determine a current density lower than brillation
threshold of the myocardium.
General Device Structure
The electroporation device is composed of two main parts:
the user interface (UI), that calculates the treatment pa-
rameters based on data inserted by the operator, shows and
elaborates data and signals measured during the treatment,