I'm Dr George Dobre, I'm a member of the Applied Optics Group in the School of
Physical Sciences at the University of Kent and I conduct research in optics
and photonics with an emphasis on photonics for biomedicine. I want to talk
to you today about some of the research that has been going on at Kent in our
research group for the last few decades but also what we're doing currently. So
the focus of our research group over time has been very much that of
providing solutions to problems that arose mainly in industry and those
solutions were mainly focused on measurement, particularly measurement of
physical parameters such as displacement, temperature, pressure, all sorts of other
parameters that could be translated into one of these and offering solutions that
can be taken up quite easily and that often meant making things robust enough
to be realised out of the lab and deployed in real-life situations. So some of the research has actually been carried out in the area of fibre
optic sensors over much of the existence of the Applied Optics Group,
starting from the 1970s onwards but the interferometer, the interferometric
techniques that we have used in order to work out things like, you know, how far is
something or how hot it is or how much is the pressure inside the chamber, those
interferometric techniques can actually also be used to map different layers of
tissue in the human body, so I want to talk to you about some of that. Now, the
interesting thing about lasers which are ubiquitous nowadays - we're constantly
surrounded by them - and this is one such example of a laser,
those lasers tend to emit light at single wavelength, single colours, and that
is something to do with the way they are built - mostly it's much easier to make a
laser that does that but we don't have much use for these types of lasers in in
the low-coherence regime that we use them in photonics and let me explain why.
If you look at the diagram on the right it represents, if you will, ripples or
interference fringes which are created at different colours and you can see that
the spacing between them is really quite different, depending on the colour, and
that's because the spacing between them is related to the wavelength. Now, if you
want to pick out a standout feature in any of those representations, the red, the
yellow and the green, you will struggle to do so. However, if you overlap them
what they all have in common is that they have a central maximum in the
middle of the pattern and so when you overlap them you will continue to have a
central maximum and then the ripples will go away and amount to nothing, all
those features will just wash out, away from the central maximum, and this is the
the key property of of light, of low-coherence light, that we are trying to
exploit in our research. As we do that, we build instruments which allows us to see
into somebody's eye for example and our instruments look nothing like the
instruments that used to be found in ophthalmology practices about 150 years
ago. So, when you examine features in a patient's eye nowadays you'd be mostly
interested in producing data in a in a number of orientations so that you give
the opthalmologist access to a richness, that they allow ... a richness that allows
them to then make an accurate diagnostic. And so I would point out to the three
different orientations that correspond to much of the data that we display and
the clear distinction should be made between the horizontal or what we call the
B scan and the transverse or what we call a C scan so that that's the B
scan in pink there and the C scan in green. And this is
particularly useful for things like the eye because there's definitely an
advantage in being able to show our types of images in the same orientation
as those that ophthalmologists have learnt about in and trained to recognise.
So much of my research has been devoted to finding ways to represent this
information, this rich information, which is really three-dimensional information
to represent that in the different orientations that would help the
ophthalmologist make that diagnosis. As you can see, you could have the
information from the eye fundus or the C scan shown in these diagrams in black
and white or greyscale, and you can also have B scan depth information, which
is often very illuminating because it really gives you access to what happens
below the superficial layers and that B scan depth information is
indicated by the coloured overlays. When you display that colour overlay under the
slice that represents the eye fundus, things become even clearer, so in this
particular case we are able to see for example a retinal defect or the retina
the retinal layers are beginning to lift up and we see
a little bit of a hole forming below the most superficial layers, and so being
able to pick out features in either of these orientations is very important,
the opthalmologist will often look for the pattern and in this particular case it's
a disease, an eye condition, called the central serous retinopathy and we are
able to see that recognisable bullseye pattern but only in the C scan, only in
the fundus image, it's not so obvious when you look at the depth scan. So,
that's one outcome that we expect but how do we ensure that we have the tools
to produce such images? Well, we have to start by building an interferometer and
really the interferometer is just a very simple device that splits light into two
arms: an object arm or sample arm which takes light and shines it onto the
feature of interest - in the previous case that would have been the retina. In the
reference arm, meanwhile, light is propagating to, typically, a mirror and it
returns and then the two arms like propagating in these terms is allowed to
interfere and so the interference pattern will tell us - if you remember the
previous slide where you saw the different fringes in different colours - it
will tell us whether we're looking at a central maximum or we're out here in the
wings and we're getting very little. So by doing that at each location on the
retina we can build an XYZ three-dimensional map of where things
are essentially. Is the reflection event happening at a particular location
or not and if it is how deep in the tissue is it?
And so we would typically detect the interference pattern with either a
dispersive method that typically spreads the spectrum onto a camera or we could
also have something called swept source which is essentially a
laser of a single wavelength that sweeps its wavelength
very many times a second, typically a few few hundred thousand times a second or
or even faster than that and in both cases we would be looking for these
maxima of interference and which we get that maximum interference we can work
out where things are. And to extend our technique, we have recently started
looking at reflection events from gold nanoparticles. Why do we say the
extension of the technique? Because, in this particular case, we are able to
produce phase maps or information about the distance travelled which is much more
accurate than without the ability to measure phase. So measurement of phase is
essentially measuring how how wide one of those fringes is and where you are on
on one of the fringes - we're getting down to very little we're getting down to
very fine displacement amounts, we're talking about nanometers rather than
microns. So gold nanoparticles have this ability to migrate in the human body to
regions where cancers are developing and they have been used in therapy because
you can you can target the area with a mirror infrared laser which causes them
to heat up - they absorb very well in that region - causes them to heat up and to
destroy cancer cells, but, more importantly, we want to know exactly
where they are and where is the highest aggregation of gold nanoparticles, so in
order to do that we have conducted a series of experiments where we place
these particles onto a slide and then illuminate them with a beam just to see
what sort of range of actual displacements we can expect. If we just
simply measure the thickness of the gold nanoparticle layer that is shown either
on the left of the picture or on the right of the
picture we can definitely see some some speckle in the image, some variation in
the phase in the phase map, whereas in the central picture we generally
shouldn't expect because that's taken from the smooth gloss surface, we
shouldn't expect to see anything other than the bullseye typical fringe pattern
that you might get as you scan. So, having these phase maps gives us confidence that
we can move towards detecting individual reflection events in depth, which we have
done, and we can see that the top of the sandwich we created by placing a glass
slide microscope coverslip in fact on top of some real pork tissue generates
three different reflection events and we have been able to measure the depths of
of all of these events and we can actually see also just down to the
nearest few microns or so where the boundaries of the glass slide are. Where
we hope to do better is now to look at those boundaries and actually fix them
to within a thousandth of the previous resolutions or just getting down from
micrometer scale to nanometer scale - we can do that and we can calibrate our
technique by using a piezo transducer whose movement we control down to the
nearest nanometer and measuring the output in phase of that transducer, which
is a graph we can see on the right of the picture there. Where we drive the
transducer with decreasing voltages, we should expect that the smallest driving
voltage the phase output will be buried in noise and that is our axial detection
limit and as I said earlier that typically a few nanometers. So we are
able to see that with nanometer precision in in the axial
direction. So, in our gold nanoparticle layer, as we produce the X&Y transversal
scan, we're actually able to build pictures of the phase and we can see
that the phase changes when the layer is illuminated with an excitation beam
which is in the near-infrared, and this excitation beam can be also tuned ... dialled
down ... in terms of power - we have looked at how little power we can get away with in
order to still produce an effect - and we found that some of the power that is
needed will ... there's sufficient ... will generate displacements of the order of
10, 20 nanometers or so, so easily picked up by our technique and those are
manifested in a change of greyscale, so when you look at those pictures and you
see that the shutter is closed, the shutter is open, that means that the
radiation or excitation beam is allowed to shine through or it's stopped by the
shutter. So we have been able to understand a little bit about thresholds
and a little bit about how long it takes for this process to manifest itself in a
change of phase. This is very exciting area of research and we're continuing
with it but I want to leave you with some images from our group and the top
row shows transversal sections through skin - in this particular case you might
see ridges corresponding to finger prints and the bottom section contains
images of the eye and in particular the retina, the central one being the macula,
which is the region of the highest sensitivity, and you can see quite good
discrimination between the layers that make make up the retina. So, thank you for
your attention.