Fine under speech beginning in
an article chemistry in two thousand and

six the University of British Columbia
in Vancouver Canada and between two

thousand and six to two thousand and eight
worked as a post doc at the Ames lab and

National Lab at the U.S. Department of
Energy and then later on motors and

the Iowa State University and later on
plans for a dog move from Iowa State

to Georgia State University with his
group not longer like twenty fifteen.

And his research group is funded by
in their chain S.F. and so on and so

forth it's a real privilege to have
let them speak as Topic think in.

Your mind.

OK so it's my great pleasure to read
of today's discussion on bio photonics

my topic is about a single particle
orientation rotation or checking So

it's a new type of spot.

Now it's not the type of sport that we
human being would do rhyming people or

baseball but I will.

Prove at the end of my top piece that she
really a type was born to happen in sales.

Not before it's brain warts
spots here I want to just

quickly go over a basic single
party go check in technique so

single molecule it is a very big for you
it's very at the was the result of this

imaging or for some of the predation
techniques so we tried to use.

Michael scopes to follow individual
molecules or nanoparticles and

now this molecules of nano particles
they have to give us some information so

we have organic dies for

us and probably things quantum dots of
gold and of particles all of these.

Can generate some kind of
optical second those for us and

scattering in those it's the microscope
can actually detect this kind of

the signals coming from our imaging probe.

Then for every moment for each image
improbable we can actually get the image

right so this is typical diffraction
limited image of four for

us a molecule all a scattering
opposite Now it's important

to actually localize these kind of
molecule particle very precisely so

we can do super localization of
this molecule a particle and

then if you do it in a time series
knowing you have to do a checking so

you had followed is molecule a particle.

In the you'll recall.

That will probably give you some insight.

In sales on surface on just
some kind of engineered system.

So it is a single particle checking
not being all research and

for science on two key words here.

So that means that you are not just
interested in the lateral movement

of these imaging probes.

Just translation motions we also
interesting rotational motions of.

Imaging probes.

To join a goal and then all rot
it's a process Monica material so

you can actually generate a very strong
signal if you use residence of a lens to

the side is imaging probe So this is
the dipole orientation of these nano

ROTT Now I actually call a technique
by five to mention a single particle

checking so I must explain what's
five to mention here you see at Y.

Z.

the reste in the nets
of these imaging probe

at the same time we also have to orientate
angles the eyes moves the angle and

also on the pol angle that these wives and
that type of orientation so together they

have five as uses that we need to resolve
in order to understand the complete

motions of this particle inside
the living sail so if we can do

that Lou we can get a lot of insights on
various different kind of biological says.

For example.

Of critical motor protein
that generate P.P. so.

This.

Actually rotates it's sent to you and
in the Gamma unit.

It's one hundred twenty degrees that each
step you generally want to be molecules

so there's a kind of rotation
happens in a living cells.

A second type of.

Rotation is cockle transpo inside
the living cell so we have to.

Form a network in inside of SEO So
in order to transport the nutrients.

All it's probably things to
different locations you need is.

System and then you also have is.

Multiple things that are basically nano
engines they work to pool their cargo and

walk across the highway so
this is a transport system now during this

transport is CA goes to show different or
and information because of the force

being applied to the Caudal
wards going it's being pooled so

we want to just by starting the or into
Chicago we're catching the older proteins.

Does walk in the in the in the living cell
not before I introduce our own technique

I want to go very briefly about the
techniques you have single molecule for

a sense in that the studies
the relative or

in patient of a for us and dipole and the.

Direction of the laser so this technique
can be used in symbol management but

in single Monaco checking live cell is
just impossible because all the frozen

background for the beauty issues so

you don't really get any information
from this kind of technique.

A nano tech these very Smadi designed.

A technique that they could
resolve in the rotation.

Just introduced so
that people actually put two for

two point four Michael acting freedom
which is forcing labeled all of the.

Rotation of these large object something
that is so you see it is the whole

thing rotates to different pages it
can resolve the rotation of the unit

no this doesn't work in live because
it requires a fixed rotation Scinto as.

So that's when we.

I studied a lab at I was
a university which is looking for

New York Asians of imaging technique so we
came out with the idea that to use these.

Nanomaterials which has a very.

Prominent resonance the fat and so.

On and all particles if you use
the residents side them and

you watch see very intense
scattering seeking though

we these kind of signal it's possible
it is followed is Madeleine and

of particles in very complex
environments and also we can do.

Something about the occasion we
can also change the shape we can

make different size of these particular so
we can change a lot of things and

we see all of these understanding
we can even do these no man of.

A nano medicine so my talk is probably
the most fundamental I'm all for speakers.

Spend most of time to talk about bio
physical implications of using go in and

goes and tools and yeah and I will talk
about how to use this go potty goes to

inhibit cancer so migration no go no rots

before us it has been used in
scattering based imaging techniques so.

Cross could be can be used to do the scary
on the phone is going on our odds they're

on the same time we do our work there's
also a technique called for those so

more imaging that can actually detect
the signal from is going in the rods so

this is basically.

Heat generated by these going in a pod
goes that can give you a second though.

Our techniques is different from phone.

Scattering technique our focus is
that she almost lifesaver checking so

we want to actually do this single
particle checking was going on rods in

living cells so we choose a technique
it's essentially a interferometry It's

called the furniture in the first contract
what the cause could be some of you may

have already used this technique in your
lab so you actually use it to look at.

You want to say is and then the.

You just overlay bit with your four as
an image so this is most typical use but

let me tell you if you really understand
the principle of the eyes to some

extreme then you can she
get really nice images for

what is going in a pod go this
images that you're on if this is for

going in a particle of forty
nanometer in diameter so

it's very small particles but you see
really high contrast images in the eyes.

Now let me introduce these the principle
of the I see very briefly so

we have the poor eyes like
come into the system and

indeed the medical school we have
to present the first along here

the law into two point privation
directions that these two prizes.

Are so many polarized and

also these two being being shifted
by a very small distance called.

These should these days typically.

Between one hundred to four hundred
enemy here now these two beings

create images that are independent
of going through a specimen

then they are arriving at the second the
prison OK so this time we actually combine

these two beings and they will move
back into the orange in the location and

then they will form one image but
because they are.

Solidly polarized so

late do not interfere these time and
then we put the analyzer year so

you have the same prize agent erosion
they can interfere and that's a reason

the rule is the I see you see those
contrasts images you see in the enhanced

A hands that dock and they're also in
the great backdrop so loose is a typical.

Highly detailed images of sales so
you see new careers and

all of it's all going to US Now let
me point the earliest three going and

overawed Gonesse fears sale in this
image as one two three here and

the reason we can put all of these go
in a pod it goes not just any features

it because gold particles if we use
the residence of a five forty nanometer

forty's fourteen enemy the spheres go
Spears you see really how conscious that

is if you switch to another resonance
wavelength say seven twenty nanometer.

You essentially see nothing so

this give us a very reliable way
to detect we're on the party goes.

If we do go in on our odds in such

even easier because going there
odds were erode Tate's That's

the whole idea of doing a rotation of
checking it's going to actually bring.

So we have is an isotropic nanoparticle
as its type or in Taishan we want

to follow it's this particle in
a live sales and we want to get all.

Information.

So in already part of our
experiment we are on lot of imaging

of these dental particles on microscope
slide so here you see two nano particles

two nano rods praise to own
microscope here and the I don't.

Know if we rotate to different
orientations zero ten twenty and so forth

you see the images of these two and then
the rods actually change periodically so

they started as completely dark images and
then they changed.

And then two completely bright.

Now at least nano particles about
twenty five would be strong as

the Spice seventy five nanometer which
seventy five is in the low as is.

And there are two optical acids
here in the Nano rots so what's.

The number which is as long as this
corresponds to a seventeen and a meter and

then there's also a show assays five
forty nine I mean a transverse mode

five forty nanometer if you compare
the images you can see when.

The same thing in America
give you a dark image here.

So these two as it's
perpendicular to each other.

Now if we rotate the particle and

then we get the intensity magic from each
device image for a particular us to see.

Those really change as
we rotate the Nano rods.

And then.

The bottom of.

This image here is that.

Image on the the I see image so it is.

Really nice change that completely
tacked it which suggest we can actually

do orientation to the nation we's
really high angle resolution so

this is type of super Rhodes which
in that we're doing in the lab OK so

different from from the Nobel Prize
winning Super as an imaging which is

emphasize on spatial resolution
he'll emphasize so anger resolution

now just were quick to show we
want to check it in three D.

So we have to orientation goes to war
as in print L'Engle in the are always

the prey elevation on the poor angle
here now because we have to praise it in

directions they create images so
we have on the dock so there's

two information to measure the intensity
and two unknown angles so we can actually

resolve both of angles using one the eyes
image so these are the most improved.

They can correlate the intensity
to these two are in teaching goes.

OK You know we have a technique
we showed that can be detected so

we actually also spend a lot of time to
figure out how to interpret the data that

we acquire from sports BERMAN So
the first feature that we can always.

Call the rotation the rate determination
so you feel you put the particle into

sale you will see actually rotates at
different speeds so here we take these

particles at two hundred frames per second
so the temporary solution of five meters

second if you go to it is really fast
you look at the Chase in the broad and

dark intensity in history so you see
the signal change is really quickly.

And then something the particle
can also slow very.

Very slowly because it
could bind to receptor

you could link to a mold approaching say
so it's motion be induced by these motors

you see a much slower rotation so
you want at you on the semi quality or

quantity of way to measure
a rotation rate so our idea is

to use all the carraige and function so we
can use these function to calculate the.

Time and we have for
the Foster with patient you can see

the ridge station time is such a shot like
for the previous example I show here.

The realization time is zero
point two zero two seconds for.

This actually you see a much larger the
station time zero point four seconds so

that gave us a way to quantitatively know.

The noise so hating the why we do it
is all I want to give you the first

biomedical implication of
our sport technique so

what you want to study rotations and
their mix of joke to be very vectors so

we use all and then over all the as
sweet a smaller system to study.

It then we can actually
put different kind.

It's modifiers to IN THE going on our odds
so we can put P.G. which is completely

new to announce the king so you will
see actually the particular speaking to

the cell membrane we can also use
the pause of each watched part of it.

And we can also use transfer and which is
approaching its neck recharged approaching

as a specific receptor in the cell
membrane we can also do peptides.

Penetrating peptide Tad's it has
a lot of a positive charge and

we can also just put.

One negative function of
group two in the pack so

then we can make it to the negative
charge so we have five different function

arise nanoparticle we see how these type
banana Pod into the cell membrane that

will give us some idea how these drug
delivery happen the on the cell membrane.

Striking the U.F.C. very different.

For what is growth rate isolation time or
the rotation speed or in the first example

I want to give you a tad functionalize
nanoparticle tad it's it's a.

Server into a cell memory
it's a city Tate's and the.

Uptake of these nano particles so
if we put the.

Particle on a cell membrane in
the beginning you see a very small

realisation time which means of relief.

After a few minutes you can see that is.

The TAL number decreases.

So.

Be established between that.

Cell membrane and off a sudden
rotation become a really really

slow that's probably the moment when the
tab that insert into the cell memory so

in the particular set of stock in
the memory is no longer rotate and

then very quickly Alison Lohman
the pocket games than a sale so

the chase stopped but
this is very different from.

What we see packed
functionalize nanoparticles So

here you see the particle keep
rotating on a cell membrane and

you see also see its rotation
speed frustrates me on a cell

membrane never getting sent to say during
our observation time to maybe two hours.

Now for transfer and this is approaching
it has a receptor binding on a cell

membrane so here you see in the beginning
is really fossil with Haitian and

the encounter it's receptor so badly
happens is slows down its rotation and

now the initial binding is not very
strong it actually got released and

you see the resume is really
faster with patients and

then a second binding happens right and
could release again and

then somehow at least time
it got to go inside so

you'd be untaught salute is crossing media
in the psychosis it's a very different

patterns of research Haitian
being detected on a cell memory

than a second feature that we can actually
get from the spore imaging experiment is

to detect the rotation mode not when
something notate we can assign three

kind of rotation modes one is called
imprinting of patients so we have these

nano ought to rotate in the horizontal
plane like this kind of rotation.

Second is all the prey notations

time rotation as such in the brain so
you'd rotates allt of the parade.

So the sort of rotation is called spin
emotions so in as it's now it's along

in the low as it's off the nettle particle
so you know things like this now this

is the more that we cannot be tap because
there's no shape change nothing happens.

In terms of the imaging so

we can only tell the difference between
the him pray in the aisle to pray notation

Now if we used to seem or
Asian just in the day or of the.

Intensity to the orientation angle you can
see if a particular does of in prayer with

patients in the price and the doc
intensity of the image of that she's

a curry did they move up and
down together.

So if you calculate appears as
creation close vision you will get

school very close to one because
the signals are highly correlated

Now if the particle does alter
prey motion Len The brought

Doc intensity that's come on
as rated as a one when Y.

increase in the other is decreasing so
if we calculate a correlation

coefficient you get something
very close to mine that one.

If there is a completely random motion you
can imagine we would just put these two

together fifty fifty then you will get
something close to zero in the courageous

call be zero because you because it
appears as a non carraige it case.

In the rotation mode.

Now we can actually do use all of the.

Rotation rate at rotation mode to study
the entire process in the psychosis

of these nano particles so
here we focus on the cross ring media and

the psychosis possibly in this
possibly when the sale one to

internalize something in their way to form
crossing coded the bot in the beginning so

the crossing will come saying to
this location they form a coat and

then the the vessel become larger and
larger and

that in the end of this process a motor
protein called dynamic comes seeing.

Structure at the neck and
it's a motion being used in the part of

the vertical being caught from the memory
and then you diffuse Insana sail and

all of these crossing code
would dissemble OK So

this is the entire process when those Atos
is across the meter in the center we want

to follow all the Nano rods through this
process and see if we can understand

the biophysical meanings of this process
especially we want to focus on the dining

hall it costs the vertical
from the memory so.

It's.

Very different from a lot of for us and.

Based imaging techniques imaging
experiments you have seeing in the past so

in always promote because gold in
a particle is number reaching so we can

follow this particle for hours as well as
the sail is active and we also can get.

A lot of a detailed information about
how these sailed the particle attached

to the cell membrane how you form a bot
how you get through the membrane in

Santa say and then be transported So this
is the entire process that happens who is.

Up to our Ok so I want to pray in
the first movie here on the and

then all right here in the red
box the first movie shows

the moments after it is narrow actually
lended on a cell membrane OK So

you see it is it brings because they
used it changes are impatient and

also see this nice nanoparticles does
it is that they're all movement so

you can do single particle
checking your fights.

Right if you look at the ice intensity
patterns you see thirty Kleek change.

Brought and that intensity
which suggest a fost rotation

if you also try to see the pattern see if
they correlate where you see it's mostly

non-cooperative case it's very random
movement so that's the initial stage

that's expected the biggest particle just
landed on a member no receptor binding

it just move around trying to find
a sweet spot and a mix the rotation mode.

After the the wall same
particle which is sitting.

Right here on our own on the.

Right of these parties you also see
a conscious image of this is that.

It is not and they're all because
they never change its contest so

our focus is on these particle it's all
and then a lot in this case the particle

actually finds is a sweet spot so
that receptor by the already happens.

In a particular rotation as you slow down
dramatically it doesn't diffuse any more

on the on the cell membrane if you look at
the trees here now in the trees actually

become much more corporate So in
the correlation coefficient will start to

increase getting close to one so this
improved patient slow rotation because.

Receptor binding on a cell membrane and
we also switched to a for instance modes.

Here we can actually tat enhanced zero for
us and protein labeled across three so

those crossing causes forms on the on
the particles the critical for

us to to visualize a crossing called
a confer possibly it's cross and

we then of psychosis and so we switch
between the for Essence and the I.C.

mode you can just see the particle is
called localized always the forest and.

Now the most interesting movie
happens here which same particle.

You see it's still slowly rotating and
then all of a sudden you freeze.

In a memory it's no rotation anymore.

That's towards the end of this I thought
this so this particle is completely

inside of that school and then allow the
motor produce associate the proteins that

comes in binds to the Vatican
essentially lock it in praise.

And then all of a sudden you
see a resume is bringing.

So this is actually.

Happens so in this sit layer and

there are other priest because I
mean induced a motion that cuts the.

Vertical from the membrane and they got
inside the sale so this is their invention

Asian and the process of this and as I sew
and as I thought is so we can I just see

this at the rotation period quiet
period that's towards the end all

of a sudden being caught and then resume
activity because now it's inside the cell.

And we can continue to follow it so

after it's being called up from
the membrane if we switch to for

a sense mode then the crossing code
disappear because this is finished and

we can also see this particle now it's
inside of sale can be transported.

So does interest there are trying to
also happen so this is that you need and

the bodies and the psychosis.

Now I want to give you a knowledge
example which is actually follow just for

the last movie I show you which it's about
the interests are a transport of cargo so

in our life we use different kind of
transportation a different age in cell.

Same thing that's very similar
we need transportation.

So that we have all of that is now what's
at form a very compromised highway system.

And we also have these multiple things
that you carry through in the cargo and

then the move along these microtubules So
this is the motor it has two hats and

then the tail that being in the cargo
case so here we have these.

We use all of the I.C. imaging also all
for us and my cost imaging simultaneously

to study it is this interest transport
process so you see the cargo.

That's attached to a number on the frozen
label the magnitude of attack and

then you see it being transported.

All the way through from
a towards the nucleus.

So this give us a very unique tool that
can actually study an intercessor transfer

we want to actually get understand
the bio physical aspects of this process

not an all out we are actually more
focused on a more interesting.

Type of a transport school
as solo transport so

this is the transport in the ass on.

In particular we want to
actually understand a pause so.

Some of the transfer or something can
be can be transferred very quickly or

very slowly lat really depend on how
frequent the cargo actually pause

in the whole how long the duration
how long the pause is OK so

if part some if a cargo pause
very frequent pause for

a lot very long time and then it's over
for speed it's that you very slow so

we want to see what's going
on in during the pause.

Now this is our initially sperm and

we are check is kind of transporting
primary neuron of cells but

this is from it's a very slow it's
thirty frames a second later on.

Which to have.

From a very much faster camera we
catch do five hundred percent and

checking all the same then
our odds in the ass OK so

you can see these numbers is
actually second so you can get.

A lot of the images we see
shot here of a time and

we can have a lot of information
about its rotation so

you see during the pause this cargo
actually changes conscious it brings.

Its Own we can also compare it
is kind of a pause during the.

A solo transport to a free diffusion
case and that's well we can use our

rotation more with the Messer to see
what the what's the difference is so

at during the pause
the we get Heidi curried

intensity we have a very high correlation
coefficient during the fried if you

look at something cold to zero because
this is really a random movement so

if we the statistics you
can see actually indeed for

all of the cases seen during a pause
You see larger records in confusion

free diffusion always get
something like smaller.

So just remind you this is

that we see the corresponds to
this high correlation coefficient.

So we can interpret what we
see in this movie as a real

live sail into Sarah transfer case so
we have here moving in this direction.

But in the cargo the try really
hard to move these cargo again so

as you go Taitz that's.

A nice area because this.

Attachment of it is coddled by the mold
approaching two in the track and

then eventually rotates in there but

what the Russian in this direction so
they continue its transport.

Now finally used two minutes I want to.

Give you one example of how we can use
these particle imaging techniques to study

to to do nano Madison So this is through
the corporation which is Professor.

At Georgia Tech.

So here we want to use going in
a particular to inhibit cancer cell

migration so
we actually have two strategies

the first one we actually put into growth
we would put the pad thai on the wall and

then our odds in the small
cone are odds and

we want to target integrate in a cell
membrane not by doing is we can actually

induce the destruction of sight of the
network not the second strategy is that.

She we put.

New.

Sequence.

All particle it targets the let me.

In the nuclear envelope increase
the nucleus different is also inhibits

cell migration.

So between two of the two of two labs
we have done a lot of the sperm and

not including the scratch as say so
basically just use to scratch in.

Sales light so when in this country
you can see after the scratch

you see an open space here and then twelve
hours later sales that you migrate back

into this area but if the sale weasel will
go in a particular zones away the new I.R.

light you can see is.

The sale cannot actually
my go to food into is this

area because it's migration is hit.

So all you saw imagery we could see
the distribution of our nano particles

inside a sail so this is different
layers we can even do three D.

image a reconstruction we can see how
these nano particles distribute it

inside is SEO and
then with from here we can Kori our.

Sale viability data migration data
to what is going in a particular So

in order to test the stiffness of the new
sail in a nuclear meant nuclear so

we can actually use the at atomic force
microscope we just touch the sail and

finally if we want to see how it is
going in a particular with the drop side

going that well we can do a super
reserved imaging to visualize this acting

aside of skin than there was so
this conventional image in my lab

we can also do super as because
the most detailed structures can see.

There's acting that way at speed
to stop it goes from is defined

fiber structure into a smear or
disrupt it structures.

Now I just.

Want.

A two actually I want to show what I
just described to you is this sort of

research and we also do catharsis
using our imaging took we have

a lot of different imaging tools
in the lab and we also do energy.

Research using these different kind of
nanomaterials And finally in the funding

agencies and also people in the work
where I have a lot of collaborators.

Thank.

You.

Here so.

The goal of.

Professor to understand the mechanism
the current stage we we we actually.

Shown the data we want to see what
kind of possibly being ordered by.

And then we identify these different
things and then we actually tried to

do imaging experiment to study the change
to these proteins so we have done.

The structure we also imaged.

So different kind of things
let's all come from our data so

there's different components
in this research I didn't show

the imaging data that's wise
it's not complete actually.

So

I take the specific targeting
of these cancer cells.

It was so.

We have started doing some.

But not in the United States.

So they have done.

So in a particular.

Show and also we service modifiers So it
is with Target this specific biomarkers.

So this is a very typical

targeting strategy we didn't
do anything extra So we just.

Targeted towards certain type of cancer so
we.

Were used to targeted Interbrand
because a lot of Kansas.

So it's a very complicated.

QUESTION So we we more focus on.

Getting our particles to in the tumor
side and then see how you inhibit the.

Migration of the cancer cell we also
focus more fundamental studies state.

Together on the fact that it's a long way
to to actually achieve the final go to.

Really cure help to cure.

This.

Thank you thank

you.