Electric pulses show promise as a new technology that can heal or kill unhealthy
cells, according to USC engineers.
The pulses are so intense they can pass virtually undetected through the outer
membrane of the cell without damaging it.
A new technology that uses electric fields to alter the “guts”
of a cell may lead to improved methods of treating diseases such as cancer and
leukemia, according to researchers in the USC Viterbi School of Engineering.
The technology, called electroperturbation, exposes cells to electric pulses
just tens of nanoseconds (tens of billionths of a second) long, said electrical
engineer Thomas Vernier, an investigator on a collaborative study to develop
the technology.
Results of the work, supported primarily by the Air Force Office of Scientific
Research with additional funding from the Army Research Office, were reported
at the national Nanotechnology 2004 conference in Boston, Mass.
The pulses are so brief and intense that they pass virtually undetected through
the outer membrane of the cell without damaging it, Vernier said. But these
fast-rising pulses pack such a powerful punch to the intracellular structures
of the cell that they can dramatically change its biochemical balance, or trigger
the start of cell death, a process known as apoptosis.
“In essence, we’re delivering thousands of volts to the cell in
mere nanosecond intervals,” said Vernier, an expert in semiconductors
who is an engineering manager at the USC Viterbi School’s Information
Sciences Institute.
“These high-frequency pulses are so short that they pass right through
the cytoplasmic membrane without altering its structure,” he said. “But
they jolt the cell’s insides and, when delivered in strong enough doses,
prompt the cell to self-destruct.”
Still a fairly new application, nanosecond electric pulsing uses “Ultra-short
Pulsed Systems Electroperturbation Technology,” or UPSET. The technology,
which has been in development at the school’s department of electrical
engineering since 2001, is supported by grants secured by the project’s
principal investigator, Martin Gundersen, a professor of electrical engineering.
Vernier and a research team from the department of electrical engineering,
the department of cell and neurobiology at the Keck School of Medicine of USC
and the Biophotonics Laboratory at Cedars-Sinai Medical Center have been testing
the UPSET technology by exposing leukemia cells to high-frequency electric fields.
The technique has advantages over conventional T-cell treatments, Vernier said.
For starters, it is noninvasive and can be delivered remotely, without attaching
contacts or probes directly to the cells. The hope is that nanoelectric pulsingone
day may replace procedures such as surgical removal of tumors or toxic treatments
such as chemotherapy.
Nanosecond pulsing is an improvement over an older technique, called electroporation,
Vernier said. Electroporation delivers longer duration electric pulses on the
order of microseconds to milliseconds. The pulses punch holes in the cell’s
external membrane, but they also can inadvertently fry the cell.
Ultra-short electric pulses deliver shorter and higher-frequency bursts of
electricity, which do not puncture the cell’s outer membrane or raise
its temperature enough to damage the cell. Instead, Vernier said, the swift
spike in voltage simply rearranges the cell’s insides, such as its nucleus
and mitochondria, without altering its outer shell.
Working in Gundersen’s laboratory on the third floor of USC’s Seaver
Science Center, Vernier uses UPSET to study the biological mechanisms that trigger
cell death.
Healthy cells automatically self-destruct when they become unhealthy or when
their numbers grow too large. Mutated cells, such as cancer cells, lose the
capacity to self-destruct and, instead, begin to proliferate rapidly. So Vernier
and his colleagues zap cells with different pulse exposures to see how the cells
react.
After exposure, the cells are treated with membrane-staining dyes and imaged
to identify internal changes. Vernier’s team also is studying the effects
of the technology on different types of cells.
“The more powerful nanosecond pulsing requires a very sophisticated solid-state
micropulse generator, a coaxial cable and special spark-gap switch, all of which
we are designing and assembling at USC,” Vernier said.
Initial observations of the UPSET system have shown that the nanosecond pulses
produce bursts of calcium inside cells within milliseconds after the pulse is
delivered, Vernier said.
“This is important because calcium ions serve as regulatory messengers
in a wide variety of processes across the physiological landscape of the cell,”
he said. “We are very interested in understanding how we might be able
to use calcium ion releases to alter specific intracellular structures.”
As the technology is refined, Vernier believes UPSET may become a more practical
and convenient tool for treating a variety of diseases. The technology also
is likely to lead to other biologically inspired nanomachines that one day may
be capable of coaxing unhealthy cells into healing or killing themselves.
Posted 11th March 2004
