Research from

the first

term.

All right.

Well thanks for having me.

This is actually the first time I'm
talking about scanning mass spectrometry

probe in front of any group
bigger than my research group and

part of that is reason for that is because
it's a very new research project and

so it's still sort of in its infancy.

I'm working on it with two professors in
mechanical engineering under a federal

support for it comes from
a number of different places.

My support comes from a pathway
into pretend dependency.

We have and
I sat through the national nanotechnology

infrastructure network and
I say that has provided

to Georgia Tech spectrometer without
which the development of this plan.

It would be much more difficult to
accomplish and it also provided a short

term plan for exploratory research too and
then there are some other support provided

by the school of mechanical engineering
from the Eugene sequined junior.

In that chair.

So the goal of the research project is to
develop a new kind of scanning probe and

I understand it's pretty general audience
I'm going to make sure everybody knows

what I'm talking about when I introduce
any kind of turn of my scanning probe.

Creating an image by basically raster
in some sort of probe or surface and

measuring the fact of an interaction so
the first one was scanning tunneling

microscopy probe when most people seem
to be familiar with these days or

atomic force microscope the probes.

So this here we're proposing is
to develop scanning probe that

serves as an ion source for
mass spectrometry.

It uses electricity and is a shell
molecules for mass spectrometry and

the result will be able to major obtain
images of chemistry in solution and

Micron resolution and

are primarily interested in looking at
applications in biology which moves us

with a solution that would be
interested in is water a queer solution

at work so I'm not going to any general
knowledge about mass spectrometry so

I briefly provide background
both on mass spectrometry and

station and then talk a little
bit about the concept that

enables creating scanning probe using
electricity and insulation which is

basically just a conceptual shift in how
electricity and it's a shame is looked at.

It's called the reverse teleco and

I'll explain how that allows us to make
a scanning probe using electricity or.

Station in the source and then in order
to sort of there's a lot of scale

phenomena that are involved in electricity
and it's nanotechnology primarily

enable this technology through the
fabrication of membranes that we use in

the scanning probe so I'll talk about how
some of the ways we're trying to do that.

So first to talk about mass
spectrometry mass spectrometry

is a method of analytical chemistry.

Basically it allows the measures the mass
to charge ratio but charged particle.

Because it does that it
can allow us to identify

compound what molecular
compounds we have in a sample.

If we're able to provide
charge of molecules and

sometimes also fragments of those
molecules to the mass spectrometer.

They need for charging the molecules
in mass spectrometry is inescapable

because mass spectrometry
performs the analysis.

Basically by combining second law of
motion forces equal to mass times

acceleration with force which
governs the motion of trollish

particles in the electric and magnetic
fields in the absence of charge on

the protocol the mass spectrometer
can't provide any information mass

spectrometer basically consists lots of
different kinds of mass spectrometers but

there are a few fundamental parts that are
always there in order to have an eye and

source the source is going to take
the molecules that are in the sample.

And it has to make sure that
they're charged it has to make

sure that they're if they were in
solution they are free of any solvent for

us to be able to identify them
using mass spectrometry and

then the mass spectrometer will
separate those charged to drive.

Based on their mass to charge ratio and

then finally there is going to be some
kind of detector those pictures for

space will tell you that a mass
spectrometer is really nothing other then

a very highly accurate scale but
it turns out that if you can.

Measure the weight of
a molecule accurately

identify the molecular formula doesn't
necessarily uniquely identify the chemical

because to get structural information
you may have to break it up and

look at what kind of fragments you get but
I have a little example here these

are all different chemicals that
had the same if you looked at just

the integral value on the periodic table
they would have the same molecular way but

if you actually look at the most
prevalent one and see what the mass

is there masses all differ slightly and
so if you can determine the masses

accurately enough you can determine
which of these chemicals you have.

So for mass spectrometry to really
be able to identify a chemical.

You need to have what's
called High Mass accuracy.

This is the Microsoft mass spectrometer
that was purchased three D.

and I grant here.

Tonics Microsoft has an accuracy and
mass spectrometry is that it's

indicated through what's called parts per
million is an indication of mass accuracy

in parts per million is defined as the
true mass of the molecule the difference

between that served mass
divided by the true million and

so high mass accuracy is usually defined
as is having an accuracy of five ppm

if you have an accuracy of five ppm you
can distinguish this mass of this mass.

So if you go back and look at
the chemicals that we had previously

they did for the first significant digits.

We can look at the seven significant
digit and distinguish the masses so

this enables you to identify
chemicals fairly accurately

provided you're able to calibrate well
enough to maintain high mass accuracy.

And so

kind of signal usually get out from a mass
spectrometers called a mass spectrum.

The mass spectrum X. axis than ours.

It's really time that it
takes science to travel

under the influence of an electric field
calibrated to give mass to charge ratio.

This is just a measure of
the intensity at different times.

So the spectrum peaks

places where we have
relatively high concentrations

mass to charge molecules with
particular mass to charge ratio.

The mass to charge ratio.

We can determine in a way our talk about
what the charge is on the molecule So

that gives us the mass of the molecule and

from that we can determine what
chemical formula is the molecule.

And so these are chemical.

Corresponding to these different peaks
that show up in the mass spectrum.

If you see just one of these peaks and
look really closely you'll see

that next to one peak you have some
other closely related peak and

these are because of the fact that
we have different isotopes different

elements that are in the chemical So
here carbon is the presence of this what's

called isotropic pattern about one percent
of all carbon is carbon thirteen and

when you put twelve carbon in a molecule
you actually get a negligible amount.

That has mass atomic mass you know you can
even see a little bit of it has a mass to

the charge on this molecule or
three then the spacing between

these isotropic peaks would be tried to
be half if it was three would be a third.

So they're looking at these
I started patterns to

ensure that you have quite
a identify the chemical and

make sure that you properly determine
the charge that the chemical.

So.

I said it's absolutely critical.

You know for in order to be able to
analyze a chemical using mass spectrometry

to first take the chemical from wherever
it is that you're looking at and

produce to try and when you want to look
at biological molecules in particular

you usually have large molecules that are
in solution and the process of taking them

and making charge dry molecules is
actually physically quite a challenge and

it was overcome by actually in
the late one nine hundred eighty S.

He won the Nobel Prize in
Chemistry in two thousand and

two he pioneered mass spectrometry.

And the the basic physical phenomena

is what's called the spectrometer
it's named after G.I.

Taylor and

determine what the characteristic angle of
this can be this is a kind of their farms

in a liquid under the influence of
a high like would feel when they

actually feel become sufficiently high not
only there's a kind of liquid form but

it comes after and then I would break down
into a spray can respond understand I

really have to understand a little
bit about electricity and is a shame.

So I'm going to talk about the physics
of electricity on a station for

a little while.

So there's a capillary it contains
the liquid that has inside the liquid

in solution whatever and you're interested
in measuring with the mass spectrometer.

Differences applied between that cap and
counter

electrode capillaries non-conducting and
the liquid is conducting then the voltage

difference can actually just be applied
between the liquid in the counter like.

But you have a focusing of the electric
field at the tip of the capillary

with its base at the rim of the capillary.

Electric plane is a should be
operated in positive or negative.

Depending upon the potential
that's applied.

So I'm going to talk about everything
could be reversed for negative and

positive electric field is going
to drive Carroll towards the code.

And it's going to drive.

Towards the away from the capillary

there's going to be
a trans electrochemical

to whichever conductor solution is in
contact with the complete circuit.

Going to be carried away and
this in this part of the reason for

the formation of the jet is
the dragon some parted on the liquid

by the motion of the Karens under
the influence of the electric field and

liquid is expelled this is positively
charged because of an excess of cat ions

and quickly succumb to instability
both the typical jet instability and

in this case it's assisted
by the propulsion present.

And as it breaks up of
positively charged droplets.

Trajectory of those droplets will quickly
be altered by the Columbia propulsion

between them.

And then as the liquid that's in
the droplets evaporates subsequent

really fission explosions of the top.

Let's fields around
the droplets that can cause.

Sufficient distance downstream
from this cone in jet.

He laughed with dry charged ions which
are suitable for mass spectrometry.

So some of the key issues essential to

his ation is the focusing
of the electric field.

At the tip of the capillary and
that electric field.

If it were just the result of
electric field it's necessary for

like to spray on as a result
of krona discharge.

This is an atmospheric pressure process.

So there is a requirement for

a high aspect ratio conductor that's
perpendicular to the counter electrode for

like to spray ionization to
occur enabling concept for

our scanning probe really nothing
other than a shift of reversal.

So the tree has been conducted for

a long time with a capillary
containing a liquid spraying into gas.

The basic concept for the scanning
mass spectrometry is the reverse

in which we take the capillary
containing the gas and

plunge it into a liquid
spray into the capillary.

The physics of this are going to be
completely unaltered in this process.

It's simply just a shift in conceptually
where liquid water gas would break.

I'll talk a little bit about what we need
to do to make sure that that the physics

of this process are actually
an altered in a little while but

once we're able to produce electricity
using this idea in the reverse term.

Then we can incorporate it into
a scanning probe by locating

membrane small capillary and

using the litter in solution
outside of the capital.

Resulting from the reverse teleco
sation to the mass spectrometer

right now working on
characterizing using a prototype.

In the prototype of the US
that specifies the active area

of the membrane that supports twenty first
is about ten microns in diameter and

the prototype right now is
enabled with a scanning

it's just a sample whatever
liquids we bring to the tip and

it's connected to mass spectrometer so

allows us to perform a tough mass
spectrometry on whatever samples we bring

in developing this scanning probe
there are two main areas that have

shown us to be developmental challenges
one of them is ion transmission.

So if you look back at the prototype.

In standard the spray just goes out
into gas and then there's usually

something called a scam that
provides the first initial barrier

between am a straight pressure and the
vacuum inside the mass spectrometer that

sucks in a portion of the ions in order to
have a skinny probe we're going to have to

contained capillary or some sort of tube
or passage to the mass spectrometer and

provide both advantages and
disadvantages we're not going any way but

we also have to make not
accidentally throwing them away but

we have to make sure that we can get them
to the mass spectrometer without losing

them to the walls along
the other main challenge and

this is the one that we're concentrating
on to talk about most today

is the membrane design and fabrication in
order to have high spatial resolution.

For the scanning probe you need to
have a very small active area for

a teleconference for
the electricity on a station.

And in order to have a stable signal.

We need to have multiple supporting Libras
telecon especially for using this for

biological applications if
you have a single home and

it becomes plug your ability to
perform any kind of experiment.

So we want to be able
to put a lot of holes

that are very very small into a very small
area because all of the holes together

are going to define the spatial
resolution of the scanning probe.

And then remember that in order to achieve
electric supply and its ration we need to

have a high aspect ratio
conductor perpendicular to account

which means the whole thing go through our
membrane which are going to define our

conductor solution for biological
applications and conductive solution.

Need to have a high aspect ratio
to be able to achieve electric

corona discharge resulting
in failure of the probe.

In this case she was we were looking for

aspect ratios least about
one hundred to one.

With holes through the membrane
better sub micro in order for

the electric field to actually be highly
focused you don't just need to have

high aspect ratio conductors but if you
have multiple conductors they need to have

sufficient spacing between them that
the electric field doesn't just sort of

see them all as a single
conductive surface.

So they need to be spaced at least
about ten diameters apart and

then finally the inner surface of
the membrane has to be hydrophobic

in order to prevent the liquid from
simply flooding the chamber basically for

the channels to define the conductor
conducting conducting cylinder.

Then the liquid can flow
through the channels and

then flood the inner
surface of the membrane.

Because the channels are so small you.

Atmospheric pressure differences
drive flow through the channel so

the inner walls of the channels
have to be hydrophilic so

you can see trying to design fabricate
membranes this is where a lot of

nanotechnology fabrication strategies and
understanding need to be implemented.

So this is just to sort of
reiterate what we're looking for

this is the active area of our membrane
we would want to have widely spaced holes

with a high aspect ratio that are also

channels to be hydrophilic But
once we get to the surface.

That's going to support
the reverse telecoms we need

to have a hydrophobic surface.

And primarily based on desire for

high aspect ratio channels
fabrication strategy is based on

membranes I talk about how they're

made in what they do for us when we
fabricate membranes we use a bad process.

It's going to create very high aspect
ratio too closely spaced for our use.

Hydrophilic surfaces all the way around.

So all that's needed in order to get the
proper surface properties is hydrophobic

of the inside of the membrane.

OK So porcelain to Mark side is
that selector chemical process for

a long time personally Mark side
membranes are primarily used now as

templates for
other nano fabrication processes.

But the basic idea of how you start with

the first step is to electric chemically
to get relatively smooth surface.

That is going to spontaneously
oxidize because it's.

With a baton and a meter to take this and
there will be some still surface

irregularities randomly spaced
on the surface of the aluminum.

Then once it's basically
fabrication of membranes.

There's a number of different assets
that are available and for each acid.

If you choose the right temperature.

And apply potential to create the right
electric field some spontaneous

self catalyzed process will occur where
under the influence of the electric field

the electric chemical reaction
in the water that will produce

oxygen ions that will migrate through
the oxide to the surface of the room and

from the limited Mark side but
they are also being enhanced dissolution

of the aluminum oxide in areas where
the electric field is more intense.

So as a result of that wherever
you have a slightly thinner.

Mark side layer you will get faster
migration oxygen I am going to mark side.

A faster dissolution
of the aluminum oxide.

So we have a regularity
in itself catalyzed.

Because the dissolution
isn't in here you end up

with thicker layers of aluminum oxide and
therefore a decrease of electric field.

So you don't start growing growing
players because the momentum

oxide there is too thick to promote
growth and growing them continue to grow.

The mechanism by which these
sort of these usually sell for

sample regularly spaced hexagonal
close pack for a nation

down far enough away from the initiation
and mechanism by which they do that.

Isn't that well agreed upon or that.

But the fact that they do that then

basically that was present originally.

If we just saw a picture of this

from the salmon will have
regularly spaced imperfections and

then we can restart the process and
that will have very regularly spaced holes

and depth to which this
process can be applied

is actually only the sort of time you're
willing to wait in the thickness of

the aluminum foil that you have the last
step is you have to come back and

you have to remove aluminum
from the backside.

And then you actually have a bunch
of cavities and finally chemically

oxide from the back of the cavity
using a person membrane so

up here this is a scanning
electron micrograph of

surface after the initial oxide.

So this shows the oxide
after the first first and

it is a shame process you have this
well ordered hexagonal pattern and

then the result after
the second oxidation process so

this is a personal
monoxide membrane said and

that produces about twenty
nanometers in diameter and

in this case it's about fifty microns.

So that's about a thousand
to one aspect ratio.

This is a process person
on the Macside membranes.

Something we're developing
we're using these

membranes to support our so

the surface of the side is hydrophilic
we can make part of hydrophobic

control far into the pores and

we still have enough of the personal
remarks available inside the channels.

There are some other options that we have
for hydrophobia zation important for

the surfaces that we have to hire from the
dielectric because if we had a bias with

a conductor then we just prevented field
focusing the fact that we're looking for.

These membranes for
the closeness of the holes to cross.

Trying to control
the spacing of the holes.

One of them is you can
perform this first step

with one chemistry class for
a class of about five

hundred nanometers apart and then perform
the second step with the second chemistry.

So that you can go with the first step and
then get small twenty millimeter

holes that we had there and
the second step and then the other thing

that I'll show you now is another sort
of process to work that we're trying to

push ahead which is basically let's see
if we can cover up some of these holes.

And the way we're trying to cover the hole
so that we are covering the hole and

using what's called a deposition where
the F. is focused on deposition.

If you're not familiar with chemical
vapor deposition if you've used

a scanning electron microscope.

Probably seeing happening.

Some light because you keep looking for
a while.

Lots of times you'll get that
black carbon showing up so

that when you move the image you see that
sort of black window still there from

whatever hydrocarbons were present.

That's not an accidental
process that's a process

that you're trying to take advantage of so
what you do is you're still uses basically

scanning electron microscope precursor

gas to control what you're going to
grow on the surface of your substrate.

And the precursor gas will eventually
surface of your sub substrate

primary electron beam from the scanning
electron microscope will produce

secondary electrons and it's wrong and
you have the proper match between

the energy of the secondary electrons and
some chemistry you want to.

Molecules you'll end up
producing the growth of

some sort of feature based
on the distribution in

the transport precursor species.

So we're just using a mix of methane and
so

the methane is the precursor of growing
carbon paper deposition and so here.

This is about two microns across so

these are actually two hundred nanometer
holes this is I've been practicing

the membranes that take me some days to
make but instead I want to approach it.

So these were these are made
with just a one step process so

you can see how these are very
very regularly spaced.

So these are without that second layer and
then a second pass to make.

But these are about two hundred
metre holes membrane and

then using with a cover all
of the holes except for

one in the middle in a certain area
to achieve the spacing necessary.

Source.

So basically mass spectrometry

spectrometry provides spectrometry

from aspect to metric analysis develop

a screening program source which would
be the scanning mass spectrometry probe.

In developing their probe the membrane
is critical element and for

us we're finding different
nanotechnology fabrication

of the fabric of the membrane for
the scanning mass spectrometry probe

everything by myself graduate students

helped with a lot of work a lot of

membrane fabrication shaft experts

position help with some of the CME
images that I showed earlier.

Thank you.

Any questions.

So they basically had an.

Dragged it to prolong the surface and
then they would rotated ninety degrees and

they would actually do for the mission.

What was ever on the tip.

For mass spec and

that was that's probably the only instance
where there's been a screening probe

used with mass spectrometry there's other
imaging mass spectrometry methods that

are scanning but they use a raster of the
laser and what's called Madley matrices

matrix assisted laser disruption
I'm ization big differences between

what you saw and what we're doing is one
that I know is a shame method you can only

you can only ionized very small
molecules so and you can't really I and

I think that one solution but it's so

so so so there's two One is that they have
to be in solution near the problem right.

So for instance when we look at
things like imaging cells and

if there's something inside the cell then
somehow we're going to have to disrupt

the cell membrane to be able to image it.

We don't look at things
the idea is like doing sort of

pro biopsy where you stick a needle inside
a cell or you can electroplate the cell.

The other limitation on being able to
see things other than they have to be

to get insulation you know the protesters
that they have to accept a charge.

And they have to take a charge
often especially in complex

solutions preferentially to other
molecules that are present.

So depending on the application there's
a good likelihood that often you'll

need to introduce some sort of
separation or selection process

on the outside of the probe if there
are certain molecules you're interested in

that you aren't getting For instance you
could allow to chemically alter the Ph.

If you're looking at proteins so

that you'll see different proteins
based on their eye so latter point.

Things that are also
going to be challenges in

identifying certain molecules or
the fact that almost all the biological

applications they're going to
be a lot of salts present.

And when you have salts they form
adults that confuse the interpretation

of the spectra so you don't know if
the charge comes from a combination of so

it was made museums and protons you want
to just be pro times that you're just

putting age classes on your molecules and

that really makes it much easier to
determine what the peaks correspond to

because everything right.

So we're hoping we're hoping and
we haven't been able to test this yet but

if we have twenty enemy you know channels
with an aspect ratio of a thousand to one.

And we're using riginal Paramount's
a billion type deposits more slowly.

If we go for a deposition.

Even though it's a vapor and
it's going to try to get everywhere.

If we protect the backside but actually
penetrate the way down is thousand to

one hundred twenty millimeter Y. diameter
channel but we haven't tested that yet.

Some of the other things that we're
using we have a silent ization

process that hydrophobia is everything and
then we have to go back and try and

fill eyes the inside of
our channel walls but.

Actually the hydrophobia zation
just inside of the membrane where

the dielectric if you can use
conductors it becomes really easy.

There's lots of things you can
splatter physically in physical a bad

place in a position.

And then hydrophobia is just the inside
of that because the whole purpose.

So that's definitely one of the areas that
we still want to show that our strategy is

going to be a factor.

Basically because apparently you
know this is trying to do what we.

I WANT IT TO BE IN ITS can
from the coding of everything

right.
So it actually application dependent

on our prototype.

We have a ten my crime.

So that would determine
the spatial resolution but

one of the questions becomes
how sensitive is the mass

spectrometer to whatever
species you're interested in.

So how strong a signal do you need as
you increase the active surface you get

a stronger signal.

Or how what kind of temporal resolution
do you need you can also get a stronger

signal just by sitting in
the same spot for a longer time.

With the Fusion isn't going to be too

bad you're not removing that much from the
solution is returning the mass spec when

you have really really small channels.

Tend to be down below
their leaders per hour.

And so the way to remember that
most species probably will go

to bed definitely having
spatial resolution.

Sort of like a skinny were
to chemical microscopy.

As opposed to scanning tunneling my
class families are just the tip size but

actually determined by transport to the
gives you the actual space resolution so

you have some boring because of transport
probable migration indication and

actually backs and doesn't play a role.

Yes.

We do what we do exactly
that we do it up here so

that I can complete it to about

two hundred degree Celsius and
the main purpose of actually D. salvation.

So if you have.

Sprayed droplets that still have to
rubber stamp the mass spectrometer

basically just probably
an enhanced get a higher number

of riots that are actually drawn I
mean you send them into a spectrum and

don't yet have good sensitivity analysis.

Yet with the membranes we
still haven't quite got

the membrane fabrication down
to the point where it's working.

Exactly how sometimes

we don't have that.

Yeah yeah yeah

OK so

here's atmospheric pressure here is

a couple millibar in the first
stage of the mass spectrometer so

in between here and
here you have all of the pressure change.

Right.
We actually have the ability through

another this gas line here
to sort of felt the pressure

get a little bit but not independently of
the rate at which we supply gas here and

actually I mean talk
about transmission of any

of the areas where we have
a conductor the assist gas and

motion of causing ions to
move with the backflow a.

Gas is critical because
otherwise the postman

will just drive all
the conducting surfaces.

So we sort of can float
this this pressure but

because the inner surface is going to be
hydrophobic we actually don't float it.

If we have a slight pressure difference.

We just have different amounts of
curvature there is a pressure difference

based on the diameter channels.

And advancing kind of the liquid
on the hydrophobic surface

which you would actually
flood the inner surface but

it tends to be much closer to the vacuum
pressure the atmospheric pressure.

So we can get relatively healthy
pressure differences across

that there's no here
actually we have nitrogen

where we can control the pressure from
atmospheric up to about five atmosphere

from this gas.

So there's two things you do.

I mean this is always an issue of mass
spectrometry people talk about you

know seeing their old samples for a week.

You have to clean in between things so

if you see this is a scanning probe then
you can sort of imagine seeing some lag.

And that'll depend sort of how much.

If you have something that's got a really
high concentration somewhere you may

kept keep seeing it for a while.

Twenty different uses one of the things
we're trying to do is just make

sure that this is cheap enough and easy
enough to make you just don't reuse it.

When you don't have to worry about
cleaning it because it can be hard

to clean out the inside of twenty
nanometer channels with an aspect

ratio of a thousand to one.

I think.