My focus is on nanotechnology and
a particular substance of nanotechnology called nanophotonics,
which deals with how light interacts with materials on the nano scale.
And what I'd like to share with you today is how light might just be
the next handy reagent for pharmaceuticals and agrichemicals.
Now before we dive into the nitty gritty details of nano photonics,
I wanted to share with you a picture of two snails that I found mating outside my
apartment about a year ago.
These snails are beautiful example of chirality,
a word that derives from the Greek word for hands.
As you can see, each snail shell has a certain twist associated with it,
in this case a right-handed spiral.
And intriguingly, this twist propagates all the way down through to the internal
organs of the snail.
Meaning that a right-handed snail is literally only a good fit for
another right-handed snail.
So if you tend to find these little guys clustering together, they're all going to
be dominated by exclusively onehandededness in their snail colony.
Now in nature, there are many molecules that,
like the snail shell, have a certain handedness associated with it.
These include molecules like DNA, which in nature is always right handed, and
sugars like glucose, which also in nature are exclusively right handed.
And also amino acids, the building blocks of proteins,
which are exclusively left handed.
Now this homochirality of nature, the fact that we don't find naturally made DNA
that's left handed, or naturally made amino acids that are right handed,
is perhaps one of life's greatest mysteries.
And one that we as chemists in the lab haven't been quite as good at reproducing.
In fact, if you turn to a typical laboratory synthesis of a molecule,
in this case I'm showing you limonene,
it turns out you wind up making mixtures of both handed molecules.
So here's a molecule for those of you who don't remember your, again,
chemistry classes.
Each vertex of the hexagon that you see up there corresponds to a carbon
hydrogen bond.
And you can imagine if you were making this molecule and you just needed to
add on that last hydrogen, where you can see kind of the bonds coming out,
it has an equal probability of going to the right or to the left.
And it turns out if that hydrogen goes to the right hand side,
then this molecules smells like oranges.
But if it goes to the left hand side, then the molecules smells like pine.
And we wind up making equal mixtures of both in a typical organic synthesis of
this particular molecule, which has a non-superimposable mirror image.
Now thinking about smells is kind of a fun example, but
it turns out that many agrichemicals and
pharmaceuticals also have a certain handiness associated with it.
And this was actually brought to prominence in the late 1960s,
when the drug thalidomide was first marketed in
Europe to treat morning nausea in pregnant women.
It turns out that if you look at the mirror image, that's non-superimposable,
and thalidomide actually induce birth defects, and
in 50% of all cases fetal death.
So a pretty catastrophic example that really brought to the forefront in
the world, and especially in the United States, the importance of testing
the effects of these molecules that seemingly are identical, but
are non-superimposable mirror images of each other.
Now if you look to the current agrochemical and pharmaceutical industry,
roughly about 50% of drugs and 40% of agrochemicals are chiral meaning
that they have a certain handedness associated with it.
And all those, more than 90% are sold as mixtures of both handed molecules.
And that's because it's so hard to separate them.
They have the same atomic constituents.
Meaning they have the same weight, they have the same electronic charge, so
it's really challenging to come up with ways to separate them.
And these would include for example the drug Advil.
Who here has taken Advil?
How long does it take for pain relief?
Yeah, I'm hearing about 20-30 minutes.
That's absolutely right.
And that's because the wrong-handed molecule essentially interferes with
the action of the appropriate molecule that combined with our cellular
receptors that generally also have a certain handedness associated with it.
So if it were sold as a pure, single-handed drug,
it would only take about eight minutes for pain relief.
Also the antidepressant Prozac is sold as a mixture of both-handed molecules,
where the wrong-handed molecule can induce migraines and heart palpitations.
And also in a number of agrichemicals like herbicides and pesticides,
the wrong-handed molecule can leave residues in soil.
Giving rise to colony collapse in bees and
in some cases organ failure in birds, fish and larger mammals.
So what my lab is trying to do is figure out if we can use light to separate
enantiomers.
Why light?
Well of course, it's a renewable resource, it's very abundant and
it turns out you can also make light into a chiral structure.
So light, for those of you who wanna go back to your physics 41 classes is
an affiliating electric and magnetic field and space and in time.
And essentially you can come up with a simple way of polarizing light so
that its electric field which I'm showing you.
Tracing out a helix in time.
So here you can see that we have a right handed spiral.
And the idea basically is that you take this right-handed helix of chiral light
and essentially it should hopefully initiate an optical handshake with your
right-handed molecules.
So that way you can physically separate the right-handed from the left-handed
molecule.
The problem is that the wavelength of visible light, which is a wavelength or
energy of light that is not going to damage your molecules,
is too big to interact strongly with molecules.
So most molecules have dimensions on the order of just one or a few nanometers or
even less.
Whereas the wave length of visible light that
we can see is about 400 to 700 nanometers.
So what we have to do is shrink the wave length of light down.
We do so by using what I call here a nanocoaxial optical fiber.
It's a lot like the coax that you would plug into the back of your cable TV.
It has a metallic core, a metallic cladding, and a dielectric ring.
In this case, that ring is just going to be air or water.
And then we'll have our chiral molecules above it.
And the idea is that if we had an array of these nano coaxial optical fibers,
we could illuminate it with circularly polarized light.
And the right handed enantiomer would basically be pulled toward right
circularly polarized light.
Passing through the air water channel enabling physical separation of
the enantiomers.
And each of those coaxes essentially acts to shrink down the wavelength of light
without changing its energy by virtue of exciting something called surface plasma.
That's probably for lecture number two, maybe later on this afternoon.
Okay, so can we make these structures?
Yes, we can, using state-of-the-art nanofabrication.
Here you can see a zoom-in of just one of the coaxial channels.
It looks kinda like a bull's-eye grading.
The grading turns out to just boost the amount of light that it's getting through
each aperture.
And if we zoom into that air channel,
you can see the thickness is just about 50 nanometers across, so
much smaller than the wavelength of light that's impeding upon it.
It's about 2,000 times smaller than the width of a human hair, and five or
ten times smaller than a typical virus.
So we're squeezing light into pretty small dimensions, but
it's still large enough to allow molecules to pass through.
And now, if we calculate the forces that a molecule would feel when light
is impending upon it, here's the pulling force as a function of x and y.
You can see from right circularly polarized light, if we have a right-handed
molecule above it, basically there's a uniformly strong pulling force.
And you'll remember that force is a vector.
It has a certain direction associated with it.
And in this case, the molecule's always going to be pulled towards that coaxial
channel, so that way it can get pushed down to the other side of the filter.
Now if we look at a right or left-handed molecule,
you can see that the force is much weaker.
And it turns out to actually be repulsive, so
that left-handed molecule will get pushed away from this all optical filter.
So the first thing we wanted to was characterize these forces.
You can see that the pulling forces are 2.5 piconewtons.
That's about 100 billion times smaller than the force exert when you're
typing a text message to your friends to say, hey, I'm at the Stanford reunion.
So again we have to turn to our nanotechnology to enable us just to
characterize the forces to make sure we can efficiently separate molecules.
And we do so using a technique call atomic force microscopy.
You can think of this technique as essentially having a diving board or
a cantilever that has your chiral structure at the end.
And all we're essentially doing is monitoring that the deflection of
the cantilever as it's moving across our sample.
So that chiral structure could be, for example, a molecule.
For visualization purposes here,
I'm showing you another chiral structure that we've just patterned at the end of
our atomic force microscope tip here just a chiral spiral.
So you can see when we turn the light on,
that the pulling force goes up compared to when the light is off.
And if we map this pulling force over just quadrant of our coaxial aperture with
extremely high resolutions, up to atomic scale resolution, you can see the pulling
force, when we have right circularly polarized light is much stronger,
when we have the right handed enantiomer compared to the left handed enantiomer.
And now if we look at all separations between the chiral structure and
the coaxial optical fiber, here's the lateral force.
It's pretty close to what we predicted theoretically on the order of
four to six piconewtons.
And you can tell for the left-handed structure, it's entirely repulsive as for
the right handed structure, it's entirely attractive.
So we're using this now to separate pharmaceutically relevant drugs
like Advil.
And in many ways, this plot is kind of the crux of my talk.
Showing that light may, indeed, be the next handy reagent to separate enatiomers.
You can think about this as light initiating an optical hand shake,
with the right-handed molecule, or if you prefer going back to our snails,
a little optical smooch hopefully enabling a healthier planet and
a healthier population.
Thank you so much for your time.