I want to tell you today about three areas of science and engineering
that I think are converging in very interesting ways.
I'm a mechanical engineer.
I've been working in robotics for over 25 years.
I've been in micro/nanotechnologies for over 15 years.
And over the past decade, since I've been here in Zurich,
I've been working more closely with biologists and with medical doctors,
and I think that the technologies we're working on
and our vision of the future has some very interesting implications.
But instead of telling you about it,
what I want to show you is a clip from a Hollywood film
that actually happens to be almost as old as I am, so ...
(Video) Man: All stations, stand by.
(On stage) (Laughter)
(Video) Man: Right. Inject.
(On stage) "Fantastic Voyage," it's a classic.
I love this movie.
Hollywood has two advantages when they make movies, versus an engineer.
They don't have to worry about physics.
They don't have actually have to make the things.
What I want to show you now
is an animation actually made for us by the Discovery Channel.
They visited my lab about a year and a half ago.
We appeared on one of their shows,
and they put together this concept of where we're heading.
And what we've been working on for several years now
have been little, what we call microrobots that we inject into your eye -
we haven't done it on a human yet,
but we inject it into your eye -
and we use magnetic fields to guide that device back to the retina
to perform certain retinal therapies, for instance delivering drugs.
You saw there, over the patient,
the sequence of electromagnetic coils that we use.
This is in a real pig's eye that you're seeing right here.
This pig's eye came from the butcher earlier that morning,
so we didn't harm any animals ourselves in making this, but -
(Laughter)
What you see is that we're able to very precisely control that device.
That device is about 0.5 mm in size,
about a millimeter long, to give you an idea of scale.
And in this next slide,
you'll see on the left is a system of electromagnetic coils we use.
We do in vivo animal trials with these.
There are eight of these coils,
we call it the OctoMag,
and we control the current in each one of those very precisely
to guide this device through the ocular cavity
back to the retina.
You'll see one of our most recent devices on the fingertip there.
That particular, we call it a microrobot;
it's about 1/3 mm in diameter, 330 microns in diameter.
And our design specs -
the reason we want it to be so thin -
it's about 1.8 mm long -
is that we want it to fit inside of a 23-gauge needle.
If it fits inside of a 23-gauge needle and we inject it into your eye,
as we remove that, that puncture wound doesn't need a suture.
It's relatively non-invasive.
You just put a little topical anesthetic, and it's done.
All the time to inject drugs to treat age-related macular degeneration -
that needle, not the microrobots,
I should say.
But that robot that I just showed you, that you see there on the fingertip,
is the biggest robot we make.
My goal is to make robots that are about 1000 times smaller than that,
something the size, for instance, of these E. coli bacteria.
These little rod-shaped bacteria are about a micron or two long.
That is about 1/100 of the width of a hair.
See those little tails coming off of them?
We'll get to that later, okay?
But before we start talking about bacteria,
I want to talk a little bit about physics and what these constraints put on us,
so we're going to do a simple thought experiment here.
Let's take a cube, okay?
It's a meter on the side.
And I don't need my calculator to do this calculation.
A meter by a meter by a meter is a cubic meter, right?
But if I take that cube and I shrink it to 10 cm -
I shrink it by a factor of 10 -
that calculation changes
because I'm taking a length by a length by a length,
and all of a sudden, it's become 1/1000th of its original volume,
and so properties that depend on volume -
for instance, mass -
also go down by a factor of 1000.
Now, if I go down another 100 times, to a centimeter,
it's gone down, now, by a million times.
And so volume -
as I said, the weight of it goes down by a million times,
but also those magnetic forces we generate on it are also going down
because they scale also with the mass of the object.
So you might say, "But since it weighs less, what's the problem?"
But now, let's think about the surface area of that cube.
It's got six sides, each side is a square meter.
It's got six square meters on that cube.
Over the volume of one, ratio of six.
But as I go down, that area is only a length by a length,
and so as I go down each order of magnitude by a factor of 10,
the importance of surface area goes up by a factor of 10.
And that causes problems, okay?
I can't make robots
and guide them with magnetic fields the way I showed you in the eye -
I can't make them any smaller than I have.
So what are some of the implications?
Well, think about a fish and how a fish swims.
A fish moves its tail back and forth in a reciprocal motion.
It's pushing the mass of fluid back and moving itself forward.
It knows Newton's first law, okay?
And so, Geoffrey Taylor, professor at Cambridge,
thought about this and published some very important papers in the 1950s,
and he made a little mechanical fish just to show how it would work in water,
and it swims just the way you'd think it would.
But if I took that fish
or I took you, and I made you 1,000 or 10,000 times smaller,
and I put you in water, all of sudden, that water would feel -
even though it has the same viscocity,
the surface effects or the drag of that water
would be much, much stronger on you.
And so what Geoffrey Taylor did -
this is a video he made in the 1960s -
is he got a vat of something very thick.
I think if you're from the UK, you know Lyle's Golden Syrup,
and I think that's what he must have used if you look at it.
So, he took his robot -
it's a little mechanical fish -
put it in there, and it doesn't go anywhere
because the fluid drag is so strong
and the mass that's pushing back is so much less than that
that it doesn't move.
And that's the problem as we go down in scale,
is that we have to rethink the way things swim
and the way things move.
Well, if you're an engineer and you don't know how to solve a problem,
what do you do?
You look at nature and think, "How did nature solve this problem?"
Nature solved this problem millions, billions of years ago.
We know there's paramecia.
You see the spermatozoa there on the right?
And they have these special little hairs on them, these cilia,
these flagella for the sperm, we call them,
that move in very interesting ways.
Now, nobody knew before 1675 that these things even existed.
Antonie van Leeuwenhoek, in Holland, was looking in his microscope,
and he was astounded
to see a world of tens of thousands of little microorganisms swimming,
and he wrote a letter to the Royal Society the next year.
They verified his results.
People were astounded, what was going on.
And what van Leeuwenhoek saw in his microscope
was the first time anybody had ever seen bacteria.
This is a graphic of one of the rod-shaped ones.
It's about a micron or two long.
And as you look at these under a microscope -
you saw the one I showed of the E.coli -
you'll notice it has a little flagella on it.
And as you look at it under a microscope,
what you see is this flagella seems to be wiggling back and forth,
but if you were able to look at it from another direction,
you realize it's not wiggling back and forth; it's actually rotating.
And Howard Berg,
when he was at University of Colorado in the early 1970s, discovered this,
and what he discovered was astounding:
nature has invented a rotary motor.
Think about it.
Where else in nature is there a rotary motor?
And Howard has been to our lab and given us some advice on what to do.
He calls these things nature's microrobots, okay?
So the body of the bacteria has sensors on it, chemoreceptors.
Those chemoreceptors communicate with the motor in the back of it,
to drive it.
That also has software in there.
The software is the chunks of DNA floating around.
They're just telling it what parts to make
to keep building the sensors it needs, the motors it needs, and all that.
And the motor is a fascinating structure.
Since Howard discovered these bacterial motors in 1973 -
which, by the way some people believe is evidence of an intelligent designer,
but I don't think most biologists believe that.
These motors are made from about 30 to 40 proteins.
They assemble into this structure
that spins up to 160 revolutions per second.
And you see on the right here, a video from Howard's lab
of fluorescent bacteria swimming at these speeds.
Remember that the size of these is a micron or two.
So we looked at this, and we were thinking,
"What can we learn from this?
How can we take advantage of this?"
So we leveraged some of our nanotechnology experience
to build something we called an artificial bacterial flagella.
Now, I can't make that motor yet.
That motor's about 45 nanometers in diameter.
But what I can make is the flagella
of a similar size and shape that a bacteria has.
And on the front of it there on the left, you'll see what looks like a head,
and what that is is actually a little piece of magnet,
and what I can do with that magnet
is I can generate a torque on it with a magnetic field,
and as I rotate that field -
and these are very, very low fields;
they're about 1000 times less than an MRI field -
they start to get it to twist,
and as it twists, it propels itself forward,
just like E. coli do.
To give you an idea of the scale we're talking about,
here's a scanning electron micrograph of a human hair;
it's about 100 microns or so in diameter.
There is the size of our smallest ABFs.
They're about 10 microns, these particular ones.
And this is the size of a red blood cell, okay?
So we're about double.
Our smallest ones are about twice the size of a red blood cell.
And here are three of them swimming together in a sort of swarm behavior.
To me, they look alive.
I get excited when we do this, you know?
(Laughter)
That's why I do robotics.
There's nothing more fun than building a machine and watching it move.
Now, you'll notice these will start to go backwards.
I didn't reverse the video; I just reversed the field.
There's some really interesting fluid dynamics to be explored here,
and that's pretty interesting.
One exciting thing for us this year was when we were in the bookstore,
we picked up a copy of the 2012 Guinness Book of World Records
and discovered that we were in the Guinness Book of World Records
for the smallest medical robot.
(Audience) Whoo!
Bradley Nelson: Being in the Guinness Book of World Records is great,
but what I'm really gunning for is,
I want to win a medal in the next Olympics,
and so we're developing synchronized swimmers.
(Laughter)
These are interesting -
What's particularly interesting about these guys
is that they're made out of a polymer.
They're noncytotoxic.
They don't kill cells;
in fact, cells like to grow on them.
And we've developed a new technology
that allows us to make some fairly arbitrary shapes here.
So in this next little video I want to show you
is one of our devices.
We put a claw on it,
and so what it can do is go around and grab these little -
these are 6-micron diameter beads,
so they're about the size of that red blood cell -
grab those, move them up in 3D, move them up and down,
and then eventually release them using these fluidic forces.
We've also been thinking about other, more serious applications as well.
Here's one of our devices.
We coated it with a fluorescent molecule called calcein.
This molecule, you're looking at it in a fluorescent microscope there.
This molecule, actually,
is the same molecular weight as a lot of chemotherapy drugs.
And on the left, you'll see some red cells that are stained red.
We discovered as we moved this bacteria near those cells and touched them with it,
the calcein actually gets taken up by the cells.
So this allows us, now, to potentially deliver drugs into individual cells
and target individual cells with this kind of technology.
The other thing that's cool -
I've only shown you a few, but we can make armies of these.
We can make them by the thousands.
We can make about one a second.
We make tens of thousands, put them in suspension.
So I think there's some interesting possibilities here
for the future of where this can go.
So let's go back to the bacterial motor.
This is a video from Keiichi Namba's lab at Osaka University.
He and his group have spent years
trying to understand the exact sequence of proteins,
how they assemble into this rotary motor.
And while I'm not at the point where I can develop the motor,
I can develop some of these parts of this device,
and so what we're hoping as we move into the future and keep going in this area,
we'll learn more and more from nature at these molecular scales
and be able to build machines that operate in similar ways
and under similar principles.
I've been very fortunate to work with some brilliant scientists,
brilliant medical doctors,
and when you're at the ETH,
the Swiss Federal Institute of Technology here -
you know, I'm an engineer.
I walk the hallways where people like Conrad Röntgen, who invented X-rays,
Wolfgang Pauli or Albert Einstein were.
It's a humbling experience.
So I take a little bit of comfort
in a quote from a famous aeronautical engineer from Caltech,
Theodore von Karman,
and von Karman said,
"The scientist describes what is; the engineer creates what never was."
(Laughter)
Okay. So.
I want to leave you with one last thought here.
This is from Richard Feynman, the famous physicist from Caltech,
who said, "What I cannot make, I do not understand."
(Laughter)
Okay. So thank you very much.
(Applause)