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New laser concept that leaves no scars
The SUREPIRL project is working to develop a new laser system to drive water directly
into the gas phase without runaway nucleation growth or shock waves and is free of
any ionizing radiation effects. This work has lead to near scar-free laser surgery and has
opened up new avenues of scientific investigation, as Dr Wesley Robertson explains
The discovery of
a new laser method to
drive water directly into the gas phase
without unarrested nucleation and shock
waves holds important implications for
surgical procedures and the detection of
single molecules. Proteins and biomolecules
need to be brought into the gas phase before
they can be analysed using mass
spectrometry, yet current methods of
performing this transformation have some
significant
limitations.
“The
main
inefficiency is in taking molecules from the
solution, bringing them into the gas phase,
and charging them for analysis,” explains Dr
Wesley Robertson. Based at the Max Planck
Institute for the Structure and Dynamics of
Matter, Dr Robertson is closely involved in
the SUREPIRL initiative, a multi-disciplinary
project developing a new laser concept which
builds on the work of Professor R.J Dwayne
Miller’s research group. “Experimental
advances in Professor Miller’s group a few
years ago allowed melting to be induced and
observed on the atomic time level with
ultrafast time resolution, this has led to the
development of a new method of
transforming a liquid or a solid directly into
the gas phase,” he continues.
A key step in this work was the
development of experimental methods to
create the first ‘atomic movies’ which
allowed researchers to study the phase
transitions between solids, liquids and gases
and study molecular behaviour in greater
depth. Out of this research, a new laserbased method of transforming a liquid or
solid directly into the gas phase without
causing shock wave damage has been
developed; an analogy can be drawn here
with the process of melting a block of ice.
“Imagine that you want to melt a block of ice
by heating it. Typically you would expect
the outside of the block to melt while the
parts closer to the centre stay frozen,” says
Dr Robertson. However, by depositing
enough energy throughout the ice, on a time
scale faster than energy redistribution, it
instead melts uniformly in a process called
homogenous nucleation. “That’s one way to
think about the work of the project,”
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continues Dr Robertson. “We can perform
an equivalent process on water rich tissue to
drive molecules into the gas phase.”
DIVE effect
The DIVE (Desorption by impulsive
vibrational excitation) effect, a novel
mechanism for laser ablation – essentially
the cold vaporization of tissue – is an
important element of the project’s research.
Previously, researchers investigated phase
transitions in metals, using electron
diffraction techniques to study matter on the
femtosecond (10-15 of a second) timescale,
work which led to some important insights.
“It was found that under certain energy
deposition conditions, the nucleation sights
are limited to a few atoms during the phase
transition, and without shock wave damage,”
explains Dr Robertson. Building on this
finding, researchers then set out to develop a
laser that could couple to water, the PIRL
(Picosecond Infrared Laser). “DIVE achieves
ablation by coupling energy through the
vibrational modes of water. The PIRL is an IR
(infrared) laser and the pulse width is really
short - it’s a pico-second (10-12 of a second)
laser,” continues Dr Robertson.
This represents a mechanism to drive a
phase transition on an extremely rapid
timescale. With the PIRL laser, energy is
focused down to the dimension of a single
cell, enabling more precise surgery. “The
energy is dumped into the water vibrational
modes in a specific volume – it goes
through the OH stretching mode of water
into translational motions which drive
tissue ablation, on a timescale shorter than
the time it takes for the heat, or other
energy, to be transmitted,” says Dr
Robertson. “The material transitions from
the solid to the liquid to gas without shock
wave damage, and without the development
of these large nucleation sites.”
This is an important issue in surgery, as
explosive growth of nucleation sites can
lead to significant collateral damage. This
has historically limited the use of lasers in
surgery, as Professor Miller explains.
“Think of the violence of boiling water, in
which small bubbles form at nucleation
sites, or defects grow and grow and then
violently collapse. This is exactly what
occurs with conventional lasers used for
surgery,” he says. “To remove material you
have to convert solid to liquid to gas and
out. Nucleation growth and collapse leads
to shock wave damage. Ultimately the
energy escapes the initially excited zone
by either shock waves or thermal diffusion
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to adjacent tissue or material leading to
massive damage. Alternatively very short
femtosecond pulses are used, but cut by
plasma formation, which is effectively
ionizing radiation. The inability to avoid
collateral damage to surrounding tissue
has greatly limited laser applications and
prevented lasers from reaching the long
held promise of reaching the fundamental
– single cell – limit to minimally invasive
surgery. The PIRL scalpel concept has
reached this limit and by simultaneously
avoiding ionizing effects, gives perfect
molecular fingerprints of the tissue for in
situ pathology and image guidance.”
The PIRL system is designed to
completely eliminate the growth of
nucleation sites and heat transfer, helping
minimise the impact of surgical procedures
on surrounding soft tissue and cartilage.
This approach leaves no scar tissue, as the
cells at the cut zone are all perfectly
viable, and there is no damage beyond the
first cell line of contact. “With this IR
laser that couples to water, you can focus
enough energy on a small volume to cause
water molecules to go into the gas phase
on an extremely fast timescale,” explains
Dr Robertson. The PIRL laser focuses
energy down to the dimension of a single
cell, operating at a pulse width of a few
picoseconds; this is shorter than the pulse
widths related to thermal transfer and
acoustic relaxation time, but not so short
as to lead to more damaging effects when
used in surgery. “It’s not so short that you
get effects like plasma formation or
multiphoton excitation, which can be very
damaging,” says Dr Robertson.
Mass spectrometry
Researchers are now aiming to explore the
wider potential of this technology, including
in both surgical and biodiagnostics
applications. While the project brings
together researchers from several different
scientific disciplines, Dr Robertson himself
is focused primarily on the development of
mass spectrometry tools. “We’re developing
new systems to use this technology and
apply it for mass spectrometry,” he outlines.
Bringing proteins into the gas phase
efficiently is a key step. “Methods like
MALDI (Matrix-assisted laser desorption/
ionization) and electrospray ionization are
used to bring proteins and other molecules
into the gas phase, so that they can be
analysed by mass spectrometry. We’re
trying to come up with a new way to bring
proteins into the gas phase for analysis,”
says Dr Robertson.
www.euresearcher.com
Currently, inefficiencies in creating and
detecting molecules mean it’s not possible
to detect every single protein, biomarker
or lipid in a blood sample. Now Dr
Robertson and his colleagues aim to
develop systems to extract proteins more
efficiently. “We’re working to develop a
system to extract proteins from water and
tissues really efficiently. We’re basically
using the laser pulse to extract intact
proteins and complexes directly from
effectively extract proteins, protein
oligomers, even whole viruses directly
from tissue and actually laser transinfect
functional viruses,” he says. “This is a
major innovation for surgical biopsies,
where now a laser can be used to sample
biomolecular signatures from tissue with
minimal colladeral tissue damage or
sample damage.”
The wider goal in this research in terms
of mass spectroscopy is to move tools
We’re developing a system in which we’re extracting
proteins from tissue and water solutions really
efficiently, and with high sensitivity
water and tissue” he outlines. “With this
approach, proteins could potentially be
extracted from tissue much more
efficiently than currently possible.”
The energy is deposited into a very
small, thin layer of water. The energy in
those vibrational modes is transferred to
the translational motions of water on the
timescale of pico-seconds, stripping away
water
molecules,
leaving
intact,
undamaged proteins. “You’re left with cold
analytes, desolvated with the water softly
stripped away,” explains Dr Robertson.
This represents a far more efficient method
of extracting proteins; Dr Robertson and
his colleagues plan to continue their
research in this area. “In a recent
publication, we showed that we could then
towards the fundamental limit of single
protein detection. With current mass
spectrometry techniques, identification is
limited to molecules that are reasonably
high in abundances; once this limitation
has been overcome, Dr Robertson says
new avenues of investigation will open
up. “We’ll be able to extract proteins more
efficiently and ionise them more
efficiently. We’ll also be able to move to
new regimes in all areas of science. We
won’t be limited any longer to only
looking at molecules in high abundance,
or molecules we know of beforehand, so
this will open up new areas of
investigation,” he outlines. All molecules
are injected into the gas phase to give a
snapshot of the composition and all
Minimally Invasive Nanobiopsy
Collector
Picosecond
InfraRed
Laser (PIRL)
Abiation
Plume
Tumour
Tissue
Healthy
Tissue
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At a glance
Project Objectives
SUREPIRL is a collaborative project in
physics, analytics, and medicine for
picosecond laser technology application in
bioanalytics and surgery.
molecular details are conserved to
uniquely identify the tissue or material;
some of these molecules play essential
roles in cells, such as signalling or
modulating neural activity, reinforcing
the wider importance of the project’s
research. “These molecules are present in
really small numbers, and we’re not really
able to detect them with current
technology, unless we really know what
we’re looking for,” continues Dr Robertson.
Project Funding
The SUREPIRL project is funded by the
European Research Council as an Advanced
Grant Seventh Framework Programme and
by the Max Planck Institute.
With this IR laser that couples to water, you can focus
enough energy on a small volume to cause
water molecules to go into the gas phase on an
Full Project Title
Picosecond Infrared Laser for Scarfree
Surgery with Preservation of the Tissue
Structure and Recognition of Tissue Type
and Boundaries (SUREPIRL)
Project Partner
• UKE Hamburg
Contact Details
Professor R. J. Dwayne Miller
Max Planck Institute for the Structure and
Dynamics of Matter
Building 99, Room O2.099
Luruper Chaussee 149
22761 Hamburg, Germany
T: +49 (0)40 8998-6200
E: [email protected]
W: www.surepirl.eu
B.J. Siwick et al., “An Atomic-Level View of Melting
Using Femtosecond Electron Diffraction,”
Science, 2003, 302(5649), 1382-1385.
M.L. Cowan, B.D. Bruner, N. Huse, J.R. Dwyer, B.
Chugh, E.T.J. Nibbering, T. Elsaesser, and R.J.D. Miller,
“Ultrafast Memory Loss and Energy Redistribution in
the Hydrogen Bond Network of Liquid H2O,” Nature
2005, 434(7030), 199-202.
signals to let the body know that there’s
been some damage, leading to scar tissue,”
explains Dr Robertson. Historically the
use of lasers in surgery has been limited,
as the shock waves and heat led to burning
and tissue damage, yet these problems
have now been resolved in PIRL, offering
an effective surgical tool to precisely
target damaged cells without leaving a
scar. “You’re basically taking this cell and
either cutting it in half, or transforming
extremely fast timescale
Scar-free surgery
Researchers in the project are also
exploring the potential use of the PIRL
laser in certain surgical procedures,
which could bring significant benefits
over existing techniques. While scalpels
and other surgical tools are commonly
used in everyday procedures, they can
also cause collateral damage to
surrounding cells. “When you cut with a
scalpel, you’re basically shearing the
flesh, you’re ripping cells apart over a
long distance from the incision site. So
the cells that are damaged send out
the entire cell into the gas phase,” says Dr
Robertson. “There’s minimal to no damage
to surrounding cells.”
The project is working in close
collaboration with surgeons at a hospital in
Hamburg to refine the PIRL laser further.
With the PIRL laser, the surgical intrusion
is of a size around just the cross-section of
a hair, and Dr Robertson says the evidence
suggests that it is a highly effective tool.
“We’ve shown in a recent publication that
the scar formation following surgery with
PIRL is minimal, even less than with the
gold standard scalpel,” he says.
Professor R. J. Dwayne Miller
Professor R. J. Dwayne Miller is the
Director of the Group for Atomically
Resolved Dynamics at the Max Planck
Institute for the Structure and Dynamics of
Matter. He was the recipient of the E. Bright
Wilson Award in Spectroscopy from the
American Chemical Society in 2015, the most
recent of many academic and professional
honours he has gained during his career.
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