Tour of UCL Biochemical Engineering Pilot Plant for prospective MSc students

hi my name’s Tarit I’m a senior lecturer
in biochemical engineering and I specialize in vaccine research and this
is Mike hi my name’s Mike hello the manager of the fermentation half of the pilot
clock wait what’s a pilot plant a very good question Tarit so a pilot plant is
kind of an intermediate size of an industrial facility in between lab scale
and full industrial scale so there are actually no pilots in the pilot plant
there are no pilots and more importantly no plants and so it’s basically for piloting
processes ah so that’s why it’s called a yes I get it so essentially once you’ve
done all your research development on the bench scale just before leaping into
commercial scale this is where you test out this idea that’s exactly good
interesting and I suppose that lots of academic departments have a pilot plant
if only they did but we are we are like a unicorn amongst Universities a beautiful
unicorn but we are the only one in the UK in the UK in Europe in Europe not in
the world not in the world no but in Europe nice so I would describe this as
the workhorse of all buy processes this is a bioreactor it’s a piece of wonder a
thing of beauty and we have many of them at varying sizes I mean we can tell you
more about the bioreactor but really that’s kind of like the first quarter of
the course so why don’t you just coming here instead and we’ll teach you all
about it but anyway where are we now Mike we are currently in the
fermentation room I guess here we’ll be talking about scaling up and scaling
down by processes looking for the range of things we can grow as we grow
different types of yeasts and other microbes algae and in a completely
separate room look like the Romanians – okay so let’s take an example let’s
imagine that I’ve created a new vaccine the brophy and ivory innate yeast do you
make that vaccine okay what are my next steps if you have this put that post is
currently in a shake class you might want to think about trying to do some
preliminary optimization in a bioreactor all right we’ll start small how small as
small as you can in this department I was forced by regret that the 250
milliliters well like these reactors over here so we have little jam jar up like these no flawlessly cuts into the
short excellent so these miniature little Aparri actors
can mimics a 100 meter bar reactor like that big cylinder thing over there as he
does that be what they’re for the beauty of these are their single use to get
thrown oil to use them that saves on cleaning also that they
are almost exactly a scaled-down and you can run more than one at once
that’s interesting so I imagine there’s a lot of engineering that goes into the
design of these things and also understanding the hydrodynamics the food
dynamics and the scaling between the small jam jar that’s all toward a large
stainless steel vessel and that’s exactly what you’ll learn to come here so in terms actually using these pieces
of equipment from the Little John Dory actors over here to be large stainless
steel equipment over there the learning that you have as part of your lectures
are supplemented by real hands-on experience in the lab itself so through
a variety of laboratory workshops and training you’ll have exposure to all
these types of equipment but in addition we also have a one-week pilot plant week
scenario and so that’s really to give you the expertise of understanding whole
bio processing so understanding how from engineering a cell to scaling out into a
reactor such as this all the way through to downstream purification will be the
main mandate of that one-week training scenario Oh about one meter 19 yes I’m I’m one
meter 75 just come over from fermentation indeed what area is this ah
so this is the downstream part of the process otherwise known as downstream
price yes interesting so let’s imagine I’ve engineered might sell it’s making
my vaccine I’ve now got lots and lots of biomass from those ba reactors in the
other room right you know I brought them here what’s next
so what from this Creek can you just give me what you’re telling me is the
magic has already happened and in this cell it deeds yeah this part
is all about getting that magic out so either the cells are your product or the
cells will make your products and if they make your product there are likely
going to be inside the cell or outside the cell let’s assume the magic or
lettuce for the vaccine is inside this out if we make that assumption we have
to break the cell oh okay I’ll be the what hammer well we know hammer BT big
and a bit too brutish I think what we would use in this case is a homogenizer
interesting homogenizer simply uses a pressure differential to cause the cell
water rupture ah right so almost through cavitation in details will then have to
burst open as it moves from a high pressure to a low pressure environment
yes exactly that I see that all right so now I’ve got my my homogeneous my broken
bits of cell also into space with some of my vaccine and of course all that
other contaminating host cell protein your nucleic acid what do we do next you
say vaccine I say magic okay so to get the magic out we need to do a the first
of all a solid liquid separation technique I would use a centrifuge just
like this one here is a thing of easy
what is this 50 that’s a motor what is the red button that stops it from your
pressure and birth don’t place it above all right so we use a centrifuge very
much like the salad spinner of biotechnology indeed separate the solid
cell debris from the liquid components yep we’ve got the liquid components my
new clay acid my host cell protein and the vaccine is still in that liquid
component how do I separate the vaccine from all the other impress impurities
very very good question now to get the mattock out yeah what you
need to do is something I like to call an chromatography and I call it that
because that’s what it’s called like yes so maybe chromatography is a way of
separating different species based on size and charge using a solvent from it
is neat also you can use not just so to talk ties but also hydrophobicity and
you can have a specific ligand that there so affinity chromatography also
cool all right so I then go through chromatography I separated my product
from my impurities yes job done indeed all you have left at the
magic you mean fill finishing yes so what is
this this is a tech town evo liquid humming robots
and what do you do with these types of liquid handling systems to these systems
are really there to bring together three strands of research we have within the
department one being using single u systems even as these little 96-well
plates are single-use yeah the other being scaling down by forces because
these are obviously much smaller than all the processes we’ve seen so far
sure and also what’s mating systems so we use a liquid handling robot to remove
any kind of human error out of the city process ice so once I’ve engineered my
cells rather than going through a 32 PI reactor then all the way through
downstream processing to try and get to my final product and I can try and mimic
that entire pilot-scale process using these small liquid handling plates in
exactly that I don’t good good it’s not true but most of the process you can
mimic using these you can definitely do cell line screening fermentations yeah
you can be filtration but not the noise it’s got plate yeah you can do
chromatography yeah again a slightly larger scale but also with liquid
handling so rather than go through the rigmarole and I guess the time and
effort of one price at time we can screen multiple factors using these
plates and try and have a much more high group of methodology of crating bats
into my case indeed so I’m sorry tastic so is it just
research scientist you get to play with it so do students also get a play with
this time I think it’s very dependent on the students but doing the research but
it if you come to zero you’ll be able to use it equipment like this to do three
to four months of X extended extensive research they’re gonna be doing stuff on
these types of systems using these types of automated systems they are indeed
their duty I said there’s a choice Abruzzi from the areas of delightful
choice you have a choice that is set out by our academic staff hmm also if it
would see there has a particular interest they can suggest amuses one of
themselves that sounds great it is should I be worried class you
should definitely wear gloves so you join us in a rest site today as we have
an MSc student just behind us it have to be quiet so not to startle them so now
are we what is this place Mike this is mammalian self the mammalian cell that
why is this different from fermentation very good question
let’s keep this separate because when yourselves kind of a longer fermentation
and therefore far easier to contaminate generally but I think we will be growing
in fermentation microbes in the Sun okay I mean so we’ve done a lot of growing in
a lot of purification work but how far do we go the other two being do we do
any salad renewing work so within the field of synthetic biology we have now
the ability to control the genome to the extent where we can literally reprogram
cells for whatever purpose we want usually we’ve chosen to use our skills
for good and so in my case where we can try and reprogram a yeast cell to try
and make a a new vaccine of interest others want to seek to re-engineer cells
to try and create next generation biofuels or enzymes to try and
facilitate chemical reactions that otherwise would be highly polluting if
we were to use a totally inorganic method
synthesis and I guess this really brings it in to how a lot of the work the
department does connects with industry as well indeed so we connect with
industry on more than one way either through collaborations for our research
students or researchers themselves or also by getting them come in to put so
they can undertake some training from us so the modular training in by process
industries or the MBI program it’s a mechanism where industrialists can come
in and not just deliver lectures to our students but also learn as well and the
great thing for our students is that they get to understand how the work
we’re doing within the department is industrial relevance and actually used
by those companies for their commercial purposes as well indeed and another
benefit is of course he gets a network with people from industry which could be
your future potential employers so basically go to NBI courses meet and
industrialists network and get a job yes that’s a good that’s a good advice