concepts & innovation in cavitation and sonoptic sciences
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On the back of this work we were able to subsequently
develop a tool to optically control microbubble placement
using laser tweezing, and to observe the interactions of
the ultrasound activated bubbles using an ultrahigh
speed camera. The figure to the left shows one such
event, whereby a small bubble (arrowed in (a)) was
placed close to a cell covered substrate and then a pulse
of ultrasound was applied. The bubble was seen to
inflate and form an invagination directed towards the
monolayer. We infer that a microjet formed, and was
issued from the bubble, causing very localised disruption
to the monolayer - usually at the single cell level. The
evolution of the microbubble can be modelled to
reasonable accuracy with a boundary element code (right
(c)) based on a modified Rayleigh Plesset equation.
However, whilst single bubbles are interesting in their
behaviour, it is only with 'clouds' of bubbles that a
clinically relevant understanding can be developed, so in
recent years we have begun extending the capability of
our pioneering 'sonoptic' laser trapping approach to
observe multiple microbubbles at MHz framing rates.
develop a tool to optically control microbubble placement
using laser tweezing, and to observe the interactions of
the ultrasound activated bubbles using an ultrahigh
speed camera. The figure to the left shows one such
event, whereby a small bubble (arrowed in (a)) was
placed close to a cell covered substrate and then a pulse
of ultrasound was applied. The bubble was seen to
inflate and form an invagination directed towards the
monolayer. We infer that a microjet formed, and was
issued from the bubble, causing very localised disruption
to the monolayer - usually at the single cell level. The
evolution of the microbubble can be modelled to
reasonable accuracy with a boundary element code (right
(c)) based on a modified Rayleigh Plesset equation.
However, whilst single bubbles are interesting in their
behaviour, it is only with 'clouds' of bubbles that a
clinically relevant understanding can be developed, so in
recent years we have begun extending the capability of
our pioneering 'sonoptic' laser trapping approach to
observe multiple microbubbles at MHz framing rates.
| Campbell CICASS Group, Carnegie Physics Laboratory, University of Dundee, Ewing Building 0-7, Dundee DD1 4HN. tel: 01382 384404 |
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The cell membrane in human cells consists of a bilayer of phospholipids just 6nm thick,
studded with a range of specialised receptors interspersed across the membrane plane. The
membrane performs the remarkable task of regulating all molecular traffic into and out of the
cytosol - and does this to such a refined extent, that water soluble therapeutic species (i.e.
many drug formulations) will not readily traverse into the cytoplasm where they can then elicit
some intended bioeffect. This is a key challenge in drug delivery.
studded with a range of specialised receptors interspersed across the membrane plane. The
membrane performs the remarkable task of regulating all molecular traffic into and out of the
cytosol - and does this to such a refined extent, that water soluble therapeutic species (i.e.
many drug formulations) will not readily traverse into the cytoplasm where they can then elicit
some intended bioeffect. This is a key challenge in drug delivery.
An initial objective for the group was thus to exploit the
power of physics in order to render the membrane into a
state of transient compromise. Early in-vitro studies showed
that the straightforward application of ultrasound in the
presence of microscopic bubbles could achieve this goal
readily. The figure to the right shows a monolayer of cells
with two individuals glowing under fluorescence, having
taken up calcein from the surrounding solution.
power of physics in order to render the membrane into a
state of transient compromise. Early in-vitro studies showed
that the straightforward application of ultrasound in the
presence of microscopic bubbles could achieve this goal
readily. The figure to the right shows a monolayer of cells
with two individuals glowing under fluorescence, having
taken up calcein from the surrounding solution.
Two cells exhibiting sonoporation
driven fluorescent uptake.
driven fluorescent uptake.
(Top) Quiescent ptically trapped microbubble
in (a) is observed to rapidly inflate and develop
a jet directed into the underlying plane of
cells. (c) Dynaflow model of the process.
in (a) is observed to rapidly inflate and develop
a jet directed into the underlying plane of
cells. (c) Dynaflow model of the process.
Junction flow focused microfluidic approach designed in-house - a
tool for developing customised microbubbles with a range of
properties and external targetting capabiltiies
tool for developing customised microbubbles with a range of
properties and external targetting capabiltiies
We are now developing a family of
microbubbles especially designed to
target cancer cells, and to transport a
range of molecular drug species into
such cells.
By achieving a better fundamental
understanding of the microscopic
mechanism of action, using our unique
hybrid imaging and trapping
instrument, we hope to develop a
strong position from which to execute a
general purpose delivery scheme
feasible across a multitude of cell lines.
microbubbles especially designed to
target cancer cells, and to transport a
range of molecular drug species into
such cells.
By achieving a better fundamental
understanding of the microscopic
mechanism of action, using our unique
hybrid imaging and trapping
instrument, we hope to develop a
strong position from which to execute a
general purpose delivery scheme
feasible across a multitude of cell lines.