Hello, and welcome to the Physics World weekly
podcast. I'm Hamish Johnston.
In this episode, I'm in conversation with Luke
Cox,
who is cofounder
and chief executive
of UK based Impulsonics.
The company spun out of the University of
Bristol in 2023
to commercialize
an ultrasonic
technology
that solves the unsticking problem,
which makes it difficult
to cultivate living cells for biological
research.
But first, an invitation to join us for
Physics World Live, which is a series of
live panel discussions
featuring experts from academia
and industry.
Quantum metrology
is our topic on the April 30,
and we will be exploring
medical physics on the July 1.
Later in the year, we will be talking
about
the commercialization
of nuclear fusion.
You can register for these events on the
Physics World website.
Just click on the Physics World live tab
at the top of any page.
Now, here's that conversation
with Luke Cox of Impulsonics.
Hi, Luke. Welcome to the podcast.
Hi, Hamish. Pleasure to be here.
So first things first, Luke. Can you describe
the unsticking
problem that Impulsonics
addresses?
Yes. Of course. So when you're growing
biological cells in the body, most of them
stick to each other in in various ways.
You know, if you think about your any
part of your body, it's made up of
thousands or millions of different cells, and all
of them stick to each other.
Typically, when we try and grow them in
petri dishes,
for testing and drug discovery,
or if you're building regenerative medicines, for example,
then you they still like to stick to
each other. Cells don't really like being alone,
and they don't like growing in unfamiliar environments.
So, when we are growing cells
in a petri dish, they will tend to
stick to plastic, and most plastics tend to
have, special coatings that enable them to
those plastics have special coatings which allow cells
to bond to them and may also bond
to each other.
But, actually,
what happens with these cells is every few
days, they're going to fill their containers, so
they will go from filling anywhere between sort
of, like, 20 to 50%
up to 80 to 90% of the surface
area of these black containers, and they then
and they then need to be unstuck
from those,
containers so that it can be moved into
a new one. And although that sounds like
a relatively simple problem, it's actually quite a
complex process. So the current approach is to
use some chemicals that sort of, like, melt
off the bonds between the cells and each
other and the plastic container.
But those chemicals, as you might imagine, are
not very good for the cells, so they
need to then be centrifuged down and to
have what liquid to move and have new
things added. And all that means is that
when you stack all of those processes back
to back, you end up with a very
complicated process that's quite user dependent, or if
you want to automate it, requires
a really large machine with actually lots of
interconnected parts all have to work perfectly in
unison every time.
I see. And is there a worry that,
you know, when you're doing all this stuff,
you're somehow,
altering the cells or damaging them, and that
could ultimately
impact
how you're using the cells and, you know,
maybe the research that's being done with them.
Yes. Absolutely. So trypsin is the most common
chemical that's used
for unsticking these kinds of cells,
and that was first used for,
cell subculturing
in 1916,
and it's actually an enzyme from the body.
But the way that
it interacts with these cells is to
literally sort of, like, cut these bonds, cleaving
is what it's called. But these surface receptors
are how cells interact with basically
every other part of the body. So 60%
of clinical drugs interact
with these surface markers.
And when you're
actually like, they regulate things like
how does a cell die. So if you're
using a drug on it, it could make
a cell more likely to die because you've
used trystin.
Ironically, for other surface markers, because they're not
all affected evenly, it could make it less
likely to die. So if you're testing an
anti cancer drug, it might underestimate the efficacy
of your drug,
or it could overestimate the toxicity effects or
underestimate the toxicity effects.
So you've got all those things. And then
when it comes to things like regenerative medicines,
cells obviously use these surface
proteins to be able to interact with our
environment. So that means modulating the immune system,
which is a lot of what
regenerative medicines do,
or actually navigating within the body, so moving
to a place where they are needed most.
So there's definitely
variable effects which are generated
from these,
from a use of this enzyme,
and we know we're disinfecting this. You know,
if you are lucky, it won't have any
impact at all, but if you are unlucky,
it's gonna have a huge impact, and it's
very difficult to quantify that impact when it's
your standard technique.
I see. And and so let let me
so
where does ultrasound or sound come into this?
I mean, when I first heard about the
company, I sort of naively thought, well, yeah.
They just sort of vibrate those cells, and
at some point,
they come unstuck. I mean, is it as
simple as that, or is it much more
complicated?
I wish it was that simple, although maybe
someone would have done it before then.
Yeah. So we do use ultrasound, and to
some extent, yeah, I'm sure you readers your
listeners will be familiar with the concept that
sound waves exert a force. That's how it
vibrates the eardrum so that you can actually
hear things, what your brain processes are sounds.
What we do is carefully control the sound
waves, so we sort of, like, create regions
of controlled high and low pressure.
And the real power that we have is
we are exerting a very direct force on
these cells. So we combine it with some
sort of, like, light chemical cues that sort
of encourage the cells to be a little
less sticky.
But the current approaches for it are usually
either you get automated shaker plates, which are
rarely used in manual processes, but they sort
of vibrate the cells around. But there, what
you're doing is applying a very indirect force
to the cells.
With
actual manual processes, often the,
the scientists have been known to sort of,
like, drum their fingers on the bottom of
a plate all the way through to sort
of literally whacking them on the table.
So there's, yeah, there's a real variability there,
and it depends on the cell type and,
and the scientists as well. So you get
you get a lot of variability. So
our process is sort of, like,
enabling people to have a much more controlled
application of force. It's applying that force much
more directly
in a way that just moving the whole
system around doesn't.
And,
yeah, enables you to sort of, like, apply
that directly.
I see. And so so when you talk
about how you apply the ultrasound, are you
do you use, like, an array
of
ultrasound transducers and, you know, you by manipulating
the signal that goes into that array, you
can focus the ultrasound, put it where you
want.
Is that is that basically how it works?
Yeah. Exactly. So we've got over hundreds ultrasound
speakers,
below these plates,
that they grow cells on. And, yes, as
you say, we're able to sort of, like,
focus the ultrasound and control it how we
want using,
well, basically mathematics,
and that allows you to if you think
about sort of like you can imagine a
sort of a curved
speaker would focus all its sound at one
point, we can achieve a very similar effect
just by applying electronic delays.
So I often think of it as sort
of surround sound for cells. If you've ever
experienced
music where you get a plane that feels
like it's going in one ear and coming
out the other, it's a similar principle just
with a lot more speakers.
I see. And,
I mean, again, just naively, you know, knowing
that ultrasound is used,
in medical applications, you know, indeed,
pregnant women will have, ultrasound
scans.
That it's it's pretty easy on cells. It's
it's not going to damage
the cells in the same way as the
as the chemicals?
Yeah. So the regime in which we work
is very safe for cells, and we've tested
that extensively. So we've done a lot of
tests to check that the cells are alive
and they're happy,
and they're, you know, not changing their health
or not changing the way that they reproduce
in any way.
Ultrasound is a very broad region,
so there are
ultrasonic systems, for example, ultrasonic baths or systems
which you use for lysing cells, which is
basically bursting cells. So cells obviously have a
lot of things inside, and you want to
measure those sometimes.
But, you know, ultrasound is such a a
broad definition. If you think about audible sound,
that can be everything from, you know, a
child's little little
piano up to a jet
engine is all technically audible sounds, but we
wouldn't say that they have the same health
effects.
I see. Okay. And and can we talk
a bit,
about the,
I suppose, commercializing
this idea.
So how how is,
how is this way of of, of freeing
cells,
being integrated into a commercially available system? You
know, what I suppose, what's your offer,
commercial offer?
So the current product that we are developing
at the moment is designed to sit inside
existing
automation systems.
So
you there are lots
in the wild at the moment of what
are known as the industry as liquid handling
robots. You can picture it just as a
pipetting robot. If you think of a a
three d printer but with a pipette instead
of an extrusion head, you get the idea
of how they work and roughly what they
look like. So our first product is designed
to integrate into one of these systems because
once you've
got your cells unstuck, what you are going
to want to do is to be able
to actually move them into a new plate,
and we're not, in the first instance, interested
in trying to
reinvent the wheel when there were a lot
of these systems out there.
The longer term vision is that we're going
to transform it into something which is more
of a a benchtop stand up device, so
we would integrate those sort of liquid handling
steps. So those are the different types of
people. So larger labs, more established companies might
already have liquid handling, and
they will probably already have some expertise in
being able to use that in house, whereas
there's a huge number of smaller labs which
are all doing this completely manually, where we
see a system being able to
actually,
you know, just be a walk up solution.
So you almost you you walk up, you
put your plate in, you press, I want
two plates out, and then you you go
and have a coffee and and come back
in ten minutes or whatever.
And that's sort of like that's where we
the two scenarios in which we can see
it working. So in some places, people want
thousands and thousands of different or probably billions,
actually, because thousands is not that many for
a plate of cells.
But, yeah, in those places, there's already liquid
handling and then expanding out into really making
sure that you can get it into every
every lab in the world.
And,
I mean, I'm guessing that, that your systems
are going to be used or maybe they're
being used already
in, research,
you know, for developing
medical applications.
And,
you know, there there's quite a bit of
regulatory,
or
you've got to get over some regulatory
hurdles, industry standards,
that sort of thing.
It it it is that something is that
an issue for you? And is that something
that you've done already? Are you in the
process of of doing that?
Yeah. So when it actually comes to drug
discovery,
so those preclinical testing of drug candidates,
there are no
sort of, like, regulations to first putting something
into the lab. So it is it is
as regulated as your toaster, so you need
your CE or your UKCA marking or your
international equivalents.
But in those cases, all of the data
that you are generating
is indicative as opposed
to actually being
clinical diagnostic data, for example.
But that's not to say that there's not
a level of reliability and trust that you
need to build up there. Obviously, scientists are
not interested in wasting their time on generating
unreliable data. It's not going to be telling
them with some degree of certainty whether or
not somebody's going to work in the clinic.
So to that extent, we haven't had to
deal with major regulatory barriers
so far for that, but we are certainly
putting in place a system
that will mean when we get to regulatory
barriers, so we'd so
actually integrating it into those regenerative medicine manufacturing
systems or, you know, we're interested in particular
in being part of personalized drug screening. So
that's when we take copies of your cells,
for example, and we'll test, okay,
what's
anti cancer drug is gonna work best for
this particular person's cancer
or and which ones are going to have
the least toxic effects, for example. And that
can be applied to all sorts of different
things. It's got had some hugely promising
early results, but it's very,
very expensive manually to get a a person
to grow all of these different types of
cells if you want to scale it up.
So then, of course, you would have slightly
different regulatory hurdles to your actual cell manufacturing
things
area.
So, yeah, that's sort of where we're looking
at. So regulation is definitely something on
a horizon, but it's not something we're having
to deal with right now. But we do
need to meet
high reliability standards and usability standards as well
because otherwise, you're just helping people generate useless
data, which nobody wants.
I see. And can can we talk a
bit about the origins
of Impulsonics?
The company,
has spun out of the University of Bristol.
I'm guessing that Bruce Drinkwater
was involved.
Yes. Bristol's
ultrasound expert. And,
I'm sure he's been on this podcast at
least once.
And I'll I'll I'll put a link to
that episode in the notes.
But I'm I'm guessing there were also
were were there some biologists
involved
in this? Can you can you talk a
bit about the academic collaboration that led to,
this the, the launching of Impulseonics?
Yeah. So as you are absolutely correct, we
spun out of the University of Bristol. Bruce
Drinkwater was one of my PhD supervisors.
So I got involved in,
the
ultrasonic tractor beam project back in
oh, now I'm testing my
self. 2016,
I think, was when I got involved in
that for a summer project, and then I
go on went on to do my PhD,
which was looking at,
optimal acoustic radiation force devices,
essentially looking at ways to
develop highly flexible systems
for particle and cell manipulation. So we've done
extensive,
collaborations with biologists
within the within the NDT group or the
UNDT group
for,
those applications. And we've done a lot of
collaboration
actually with,
I think he's now assistant professor James Armstrong,
then a postdoc at Molly Stevens Group, who's
quite a prestigious,
bioengineering
professor over at
Imperial College London, I want to say.
So, yeah, we worked quite a lot with
James and with other biologists
on various
applications.
One of the really nice things, as you
said earlier, is that we know that ultrasound
is very compatible
with biology and in terms of length scales
as well in terms of where it works.
There was sort of a lot of work
done and won the Nobel Prize not too
long ago on using optical tweezers,
which max out in a size at about
the size of one single cell, and ultrasound
can go down to about one single cell
and up to the scale of millions.
So that was where there was a real
sort of, like,
lot of interest in where we have a
lot of needs to move millions of cells
at a time.
So we worked with James Armstrong.
We've been doing some collaborations with him in
terms of characterizing acoustic devices and how we
design them
and that sort of work. And then as
we came to the end of my PhD,
which had been more about developing
ultrasonic techniques,
we then started to focus more on those
collaborations and building systems that would work specifically
for the needs of biologists.
So there was sort of, like, two years
there where I was working grant to grant
within the University of Bristol and also doing
some part time work with some other I
worked for Ultra Leap for a little bit
part time on they use ultrasound for haptic
feedback in air, so a very different application,
but some
comparable skill sets. And,
yeah, that was something that we've been working
on, basically validating this technology, showing that it
worked on cells,
achieving various manipulation techniques,
and also doing some market research with some
of Innovate UK schemes to be able to
actually understand what are the really big
problems that people are trying to solve
with,
or
not with ultrasound, actually, the opposite of that.
People problems that people are trying to solve
that our technology would be applicable to.
And that was how we identified this cell
unsticking or cell passaging is the name of
the whole process as a key area where
there was a real unmet need but but
our technology could meet.
And and so,
Luke, what's next,
for the company? You you you mentioned earlier,
applications,
you know, sort of more clinical
applications
of the technology.
So I'm guessing that's one thing that you're
pursuing actively at the moment. But are there
any other
applications of this unsticking process,
you know, maybe not related to
biology
or medicine
that,
that that that you could pursue?
So I think the company's focus for now
is probably going to be on the the
biotechnology
aspects of it,
not exclusively related to the unsticking. So there's
replacement of centrifuges for certain applications because we're
able to manipulate cells within the well. There's
also the manipulation of these larger structures called
organoids, which can be made up of millions
of cells, so they can be up to
tens to hundreds of microns, even up to
a couple of millimeters in diameter.
And those are all things for which they
aren't great solutions for manipulating it.
We're probably
not in the short term looking at
nonbiological
applications, but I do still think that there
was some interesting and exciting applications of this
kind of technology
in material science, particularly being able to align
small particles within, for example, a composite structure.
So that allows you to get
anisotropic,
so directionally stronger in one direction, say, x
rather than y.
So getting that anisotropic strength is something that's
been shown in biotechnology using ultrasound and indeed
in composites. So there's some overlap there, and
I think that could be quite an exciting
field if you wanted to do some really
high precision
engineering, which could also be combined with three
d printing, for example.
So I think there's a lot of scope
for these things, and, of course, there's some
really exciting work that people have been doing
to actually levitate particles in air, which has
some broader scientific applications.
One of our engineers, Adam, actually at one
point did some work on, like,
levitating
to view proteins and things like that.
And that was, I think, at one point
used to optimize the production of chocolate, so
you never know where it's going to go.
But, yeah, that's probably
our goals for the moment are probably focused
on expanding our position
within
the biotechnology market, and that's sort of where
we've optimized for.
And if I can ask you one final
question, Luke. We're you know, here at Physics
World, we're very interested in,
careers.
And I I I know strictly strictly speaking,
you you you you're not a physicist. But,
you know, we'll we'll make you an honorary
physicist for that for the purposes of this
of this podcast.
And I I'm just curious about, you know,
when you were doing your PhD,
did you did you have working for a
startup
in mind?
Is that something that you're interested in right
from the beginning, or did it sort of
evolve as you were sort of seeing the
research that was being done in Bruce's lab
and maybe some other labs that you thought,
okay. I can I can go with this,
you know, once I'm once I've finished, I
can I can commercialize this technology?
Where where where when did you get the
idea to,
to work, you know, to to to get
involved in a start up rather than working
for a
established company?
So I think the idea of working for
a start up to some level was always
something that was on my radar. I think
it's a little bit difficult
not to have it on your
radar in in the modern world if you're
studying some kind of a technology, but, of
course, lots of people don't go and do
it. I think for me, one of the
big influences was as part of my undergraduate
degree, I went and did three months working
for building services engineering firm called WSP.
And
I I didn't find that
as
exciting, and maybe I was very interested in
working with cutting edge. And building services engineering,
of course, is hugely important,
and it is everywhere.
And if that makes it a very, very
stable career path,
and, of course, people do exciting things in
it. But I realized for me, I
was really interested
in being the first person to do things
and to do things that were really cutting
edge.
And looking around at the world, I saw
that a lot of the stuff that was
being done right on the cutting edge was
being done by startups. I think of a
lot of limp the influence,
I have to probably give to Ultra Leap
was one of the companies based in Bristol,
which had previously spun in part out collaboration
between the, Bruce Drinkwaters Lab and the Bristol
Interactions Group that I also worked for. So
I always had an awareness that startups were
doing interesting things
in my fields,
if that makes sense.
So that was something I'd sort of, like,
looked at and gone back. Oh, that's quite
interesting.
And then as I did my PhD,
I I became increasingly convinced that there was
something valuable
here, but
we,
there were problems that weren't being solved, that
could be solved with this technology, and someone
was going to have to do it.
And
I figured I would I would give it
a go and
see if I could.
So that's sort of where it came from.
I think throughout my PhD, I was definitely
aware of startups. So, obviously, we're not the
UltraLeap is not the only one to have
come out of our research group. There's another
group, company called InductorSense,
which does these little
sensors that are almost
they're like a sticker that you can put
onto
a a pipe, and then you can just
tap a sensor against it, and it
activates it and then gives you a a
thickness measurements.
So you get really repeatable thickness measurements, for
example. So I could see there was also
a broad range of things, like, didn't just
have to be, you know oh, UltraReach was
very much focused on the human computer interactions,
which fits
maybe within the more sort of,
sexy Silicon Valley image of a startup, whereas
InductorSense is more focused on a much more
hardware industrial
world, you know, something that's perhaps not quite
as
not quite as slick as Uber, for example,
but it's,
still very important, and it showed that, actually,
you can get startups existing within a whole
range of different worlds
and solving solving very different problems and offering
very different value propositions to the world.
So,
yeah, it was just I think it was
something I was always interested in doing
something really cutting edge, and I eventually came
to see
being part of a start up as
a way of doing that. And for an
extended period of time, I guess I was
just
seeing if it would work and,
you know, knowing that there were other options
available
for
people with technical knowledge as I did as
I went along.
And what what would your advice be to,
you know, somebody who's doing a degree in
physics or maybe they're doing a PhD?
Is the, you know,
the the world of biophysics,
you know, as applied to medicine,
it it
it I mean, is that a really growing
field? Is is there a lot of growth
there? Do you think that that's where that
would be one place where a physicist, you
know, could look for a career, you know,
either in a start up or in a
in a larger company?
Yeah. Absolutely. I mean, I think what's very
interesting
about
biotechnology,
particularly at the moment,
is that there's this huge drive for data
quality
because a lot of people are looking at
their AI models and they're looking at their
data and they're going,
a lot of this data isn't that good.
I'm going to
just feed some noise into this model. I'll
need to generate new data, and that was
something that was actually recognized of a The
UK's AI for science strategy recently. But there's
also
a huge amount of opportunity, I think, at
the moment,
for not just
quantity and quality of data data, but actual
depth of data, looking for new types of
data, more predictive data,
and new ways of engineering things. And I
think there's also a lot of interesting
physics based problems,
to be solved in that world, particularly when
we look at regenerative medicines and cell therapies.
You know, I speak a lot about regenerative
medicines in particular because
that is a
emerging linguistic distinction from cell therapies which tend
to be more focused on things like t
cells, which are grown in suspension. So they
grow floating because they would normally sit in
the blood.
We have applications in that area, but
for simplicity of the explanation.
So that's something but there's definitely
a lot of growth and a lot of
interest in that and actually those interactions of
how can we build
new drugs, how can we build new medical
devices, and in particular,
there's a lot of interest in making bringing
things much closer to the patient, which is
maybe where physics comes in at the most
interesting level. So one of the most interesting
examples of this I can give is there's
a company called Siloton, which is based in
The UK, which is based in Bristol,
and they use,
quantum chips to be able to actually
measure how your eye is degrading. So for
people who've got eye degradation conditions, for example,
it transforms it from something that only gets
sort of, like, infrequently tested in the hospital
into something that can actually be located very
close to the point of care.
So that actual
creating
much better
diagnostics and putting it really close to the
point of care is
hugely important
and being able to put more sensors into
wearables, for example. You know? I look at
I've got a a smart tracking watch and
the the blood flow measuring techniques were, you
know, originally used on on pilots in World
War two clicked onto the ears, but actually
being able to reengineer that to be able
to fit into a watch and just be
a,
yeah, single single sided sensor and all that
sort of thing. That's there's a lot of
physics there, I think, particularly in the census
space would be where I'd be looking as
a physicist interested in that world. And, of
course, it's hugely rewarding because you are helping
to improve people's lives.
That's great. Oh, so some exciting stuff there.
I should point out that, I believe we've
covered,
well,
possibly your work, but definitely somebody in Bruce's
lab's work on acoustic tweezers.
And so I'll put a link in the,
in the podcast notes for that. And I'm
pretty sure that the folks from Siloton
have been on the podcast as well. Oh,
well, go and listen to them. You can
find out what I'm saying what's wrong.
It is a small world. So I'll put
some I'll put the notes I'll put a
link to that in the notes, as well.
Well, Luke, thanks so much for coming on
the podcast and talking about impulsonics.
It's a it's a fascinating story,
and, we wish the company very well.
Thank you, Hamish. Thanks for having me.
That was Luke Cox of Impulsonics.
Thanks, Luke, for a fascinating discussion.
Don't forget to check out our series of
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I'm afraid that's all the time we have
for this week's episode.
I'm Hamish Johnston, and our producer is Fred
Isles.
The theme music for our podcasts
is called one three seven, and it was
composed and performed
by the physicist
Philip Moriarty.
We'll be back again next week.