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Biomedical Applications of High Energy Ion Beams
Focussed beams of MeV ions usually, although not exclusively, protons can
be used to address three main themes, with respect to research in the life
and medical sciences. These will be dealt with, in order, in the following
sections:
- ion beam analysis
- cell and tissue irradiation studies
- nano-lithography, nano-machining and nano-structuring
For ion beam analysis the major breakthrough came in the early 1980's when
Dr John Cookson at Harwell and Drs Geoff Grime and Frank Watt at the University
of Oxford designed and engineered lens systems which were capable of
focusing an ion beam down to 1um in diameter in vacuo. By scanning the
beam across a sample and by having a number of detectors in the chamber it
is possible to conduct simultaneous PIXE (particle induced X-ray emission).
RBS (Rutherford Backscattering), STIM (scanning transmission ion microscopy)
and SEM imaging of the sample. The combination of these techniques together
with the mapping capability allowed surface elemental distributions (detection
limits of a few ppm) and elemental depth profiles and thicknesses to be mapped
for all elements above helium in the Periodic Table.. Since then a
wide range of biological and medical materials have been examined by this
technique. As the samples were usually freeze dried before analysis in vacuuo
there has always been the question about how representative they are of the
same material in air or medium. Thus, the obvious next step is to take the
beam outside the vacuum chamber and examine the samples in vitro.
External ion micro-beams are already used for the analysis of art and archaeological
artefacts with a beam diameter of 20 - 200 um; the challenge for biological
and medical samples is to first reduce the beam size to less than 1 um so
that sub-cellular structures can be analysed and then to present the samples
to the beam so that the cells remain in a fixed location.
Considerable expertise has been developed in cell positioning by those studying
cell irradiation. Here individual cells, in a population of cells in
culture, are targeted with a precise number of ions. The response of
the cells to precisely controlled doses of radiation, at specific parts of
their structure, at specific points in the cell cycle, enables the mechanisms
by which ion beams interact with living cells and tissues to begin to be determined.
This is the only way of obtaining this type of information. The research
is important as it is a route to the development of improved strategies for
cancer treatment and better estimates of the risks associated with occupational
and environmental exposures to ionising radiation.
Despite considerable interest, worldwide, only two microbeam laboratories
are in routine operation for this purpose; these are located at the
Gray Cancer Institute
(GCI), North London and Columbia University, New York. Other microbeam
laboratories for radiobiological research are however under discussion or
construction in France, Italy Germany, USA and Japan.
Current technology for cell irradiation, uses collimated protons (<±2um
diameter beam) and makes use of micro positioning to enable automatic targeting
of single cells. By focussing the proton beam down to sub micron dimensions,
scanning it across the sample and making use of new developments in image
recognition it should to realise beam diameters of 50-100nm, irradiate 100,000
unstained cells per hour (maximum at present is 10,000 stained cells per hour)
and use the equipment in two modes: single ion for cell irradiation studies
and continuous flux for ion beam analysis.
The decrease in beam diameter will allow much smaller structures within
the cell to be targeted and analysed. The rapid scanning will make
it feasible to routinely study biological endpoints that occur infrequently,
such as cell transformation and will also enable more cell lines to be investigated.
Furthermore, it will facilitate studies on synchronised cell phases where
rapid scanning is vital as a phase can be complete in ~1 hour. The ability
to undertake high resolution ion beam analysis, will allow parallel studies
of elemental changes within the cell and at the cell surface, for example
shifts in intra-cellular trace element distribution.
Nano-machining using ion beams is the newest area of research using micro
and nano focussed MeV ion beams. The nano-machining of soft solids by
high energy ion beams was pioneered By F Watt and G Grime in Oxford and is
now being pursued in Singapore (F Watt) and Surrey (G Grime). Preliminary
work, on tissue scaffolds has shown that tissue can be successfully grown
on three dimensional structures fabricated on a substrate using ion beams.
Similarly, the ability to form complex three dimensional structures, with
a high aspect ratio, relatively quickly, opens up applications for drug release
devices, biosensors, lab on a chip and nano-reactors etc.
A
Research Network on the Bio-Medical Applications of High Energy Ion Beams
has recently been funded by EPSRC.
A EU Marie Curie Research Training Network
CELLION
has also been funded. The Network involves 9 European laboratories
and is aimed at studying single cell irradiation and analysis and modelling
the response of cells to radiation.
A separate application, to EPSRC is in progress on nano-lithography and
nano-machining
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