16:47
TEDxBoston 2009

George Whitesides: A lab the size of a postage stamp

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Traditional lab tests for disease diagnosis can be too expensive and cumbersome for the regions most in need. George Whitesides' ingenious answer is a foolproof tool that can be manufactured at virtually zero cost.

- Chemist
In his legendary career in chemistry, George Whitesides has been a pioneer in microfabrication and nanoscale self-assembly. Now, he's fabbing a diagnostic lab on a chip. Full bio

The problem that I want to talk with you about
00:15
is really the problem of:
00:18
How does one supply healthcare
00:20
in a world in which cost is everything?
00:24
How do you do that?
00:28
And the basic paradigm we want to suggest to you,
00:30
I want to suggest to you, is
00:32
one in which you say that in order to
00:34
treat disease you have to first know what you're treating --
00:36
that's diagnostics -- and then you have to do something.
00:40
So, the program that we're involved in is something which we call
00:42
Diagnostics for All, or zero-cost diagnostics.
00:45
How do you provide medically relevant information
00:49
at as close as possible to zero cost? How do you do it?
00:52
Let me just give you two examples.
00:56
The rigors of military medicine
00:58
are not so dissimilar from the third world --
01:02
poor resources, a rigorous environment,
01:04
a series of problems in lightweight, and things of this kind --
01:07
and also not so different from the home healthcare
01:11
and diagnostic system world.
01:14
So, the technology that I want to talk about
01:17
is for the third world, for the developing world,
01:20
but it has, I think, much broader application,
01:23
because information is so important in the healthcare system.
01:25
So, you see two examples here.
01:30
One is a lab that is actually a fairly high-end laboratory in Africa.
01:32
The second is basically an entrepreneur
01:37
who is set up and doing who-knows-what in a table in a market.
01:39
I don't know what kind of healthcare is delivered there.
01:43
But it's not really what is probably most efficient.
01:46
What is our approach?
01:51
And the way in which one typically approaches
01:54
a problem of lowering cost,
01:57
starting from the perspective of the United States,
02:00
is to take our solution,
02:03
and then to try to cut cost out of it.
02:05
No matter how you do that,
02:07
you're not going to start with a 100,000-dollar instrument
02:09
and bring it down to no-cost. It isn't going to work.
02:11
So, the approach that we took was the other way around.
02:14
To ask, "What is the cheapest possible stuff
02:17
that you could make a diagnostic system out of,
02:19
and get useful information,
02:22
add function?" And what we've chosen is paper.
02:24
What you see here is a prototypic device.
02:27
It's about a centimeter on the side.
02:30
It's about the size of a fingernail.
02:32
The lines around the edges are
02:34
a polymer.
02:36
It's made of paper and paper, of course, wicks fluid,
02:38
as you know, paper, cloth -- drop wine on the tablecloth,
02:42
and the wine wicks all over everything.
02:46
Put it on your shirt, it ruins the shirt.
02:49
That's what a hydrophilic surface does.
02:51
So, in this device the idea is that you drip
02:54
the bottom end of it in a drop of,
02:56
in this case, urine.
02:58
The fluid wicks its way into those chambers at the top.
03:00
The brown color indicates the amount of glucose in the urine,
03:04
the blue color indicates the amount of protein in the urine.
03:08
And the combination of those two
03:11
is a first order shot at a number of
03:13
useful things that you want.
03:15
So, this is an example of a device made from a simple piece of paper.
03:18
Now, how simple can you make the production?
03:21
Why do we choose paper?
03:24
There's an example of the same thing on a finger,
03:26
showing you basically what it looks like.
03:29
One reason for using paper is that it's everywhere.
03:31
We have made these kinds of devices using
03:34
napkins and toilet paper
03:36
and wraps, and all kinds of stuff.
03:39
So, the production capability is there.
03:41
The second is, you can put lots and lots
03:44
of tests in a very small place.
03:46
I'll show you in a moment that the stack of paper there
03:48
would probably hold something like
03:50
100,000 tests, something of that kind.
03:52
And then finally, a point that you don't think of so much
03:55
in developed world medicine:
03:58
it eliminates sharps.
04:01
And what sharps means is needles, things that stick.
04:03
If you've taken a sample of someone's blood
04:06
and the someone might have hepatitis C,
04:08
you don't want to make a mistake and stick it in you.
04:11
It just -- you don't want to do that.
04:13
So, how do you dispose of that? It's a problem everywhere.
04:15
And here you simply burn it.
04:17
So, it's a sort of a practical approach
04:19
to starting on things.
04:21
Now, you say, "If paper is a good idea,
04:24
other people have surely thought of it."
04:27
And the answer is, of course, yes.
04:29
Those half of you, roughly,
04:32
who are women,
04:34
at some point may have had a pregnancy test.
04:36
And the most common of these
04:38
is in a device that looks like the thing on the left.
04:41
It's something called a lateral flow immunoassay.
04:44
In that particular test,
04:46
urine either, containing
04:48
a hormone called HCG, does or does not
04:50
flow across a piece of paper.
04:53
And there are two bars. One bar indicates that the test is working,
04:55
and if the second bar shows up, you're pregnant.
04:59
This is a terrific kind of test in a binary world,
05:02
and the nice thing about pregnancy
05:05
is either you are pregnant or you're not pregnant.
05:07
You're not partially pregnant or thinking about being pregnant
05:09
or something of that sort.
05:11
So, it works very well there,
05:13
but it doesn't work very well when you need more quantitative information.
05:15
There are also dipsticks,
05:18
but if you look at the dipsticks, they're for
05:20
another kind of urine analysis.
05:22
There are an awful lot of colors and things like that.
05:24
What do you actually do about that in a difficult circumstance?
05:27
So, the approach that we started with is to ask:
05:30
Is it really practical to make things of this sort?
05:35
And that problem is now, in a purely engineering way, solved.
05:39
And the procedure that we have is simply to start with paper.
05:43
You run it through a new kind of printer called a wax printer.
05:47
The wax printer does what looks like printing.
05:50
It is printing. You put that on, you warm it a little bit,
05:53
the wax prints through so it absorbs into the paper,
05:56
and you end up with the device that you want.
05:59
The printers cost 800 bucks now.
06:01
They'll make, we estimate that if you were to run them 24 hours a day
06:05
they'd make about 10 million tests a year.
06:08
So, it's a solved problem, that particular problem is solved.
06:11
And there is an example of the kind of thing that you see.
06:14
That's on a piece of 8 by 12 paper.
06:16
That takes about two seconds to make.
06:19
And so I regard that as done.
06:21
There is a very important issue here,
06:23
which is that because it's a printer,
06:25
a color printer, it prints colors. That's what color printers do.
06:28
I'll show you in a moment, that's actually quite useful.
06:31
Now, the next question that you would like to ask
06:35
is: What would you like to measure? What would you like to analyze?
06:38
And the thing which you'd most like to analyze,
06:41
we're a fair distance from.
06:44
It's what's called "fever of undiagnosed origin."
06:46
Someone comes into the clinic,
06:50
they have a fever, they feel bad. What do they have?
06:52
Do they have T.B.? Do they have AIDS?
06:54
Do they have a common cold?
06:56
The triage problem. That's a hard problem
06:58
for reasons that I won't go through.
07:00
There are an awful lot of things that you'd like to distinguish among.
07:02
But then there are a series of things:
07:05
AIDS, hepatitis, malaria,
07:07
TB, others
07:09
and simpler ones, such as guidance of treatment.
07:11
Now even that's more complicated than you think.
07:15
A friend of mine works in transcultural psychiatry,
07:18
and he is interested in the question of
07:22
why people do and don't take their meds.
07:24
So, Dapsone, or something like that,
07:27
you have to take it for a while.
07:29
He has a wonderful story of talking to a villager in India
07:31
and saying, "Have you taken your Dapsone?" "Yes."
07:34
"Have you taken it every day?" "Yes."
07:36
"Have you taken if for a month?" "Yes."
07:39
What the guy actually meant
07:41
was that he'd fed a 30-day dose of Dapsone
07:43
to his dog, that morning.
07:45
(Laughter)
07:47
He was telling the truth. Because
07:48
in a different culture,
07:50
the dog is a surrogate for you,
07:52
you know, "today," "this month," "since the rainy season" --
07:54
there are lots of opportunities for misunderstanding,
07:57
and so an issue here is to,
08:00
in some cases, to figure out
08:02
how to deal with matters that seem uninteresting,
08:04
like compliance.
08:07
Now, take a look at what a typical test looks like.
08:10
Prick a finger, you get some blood,
08:14
about 50 microliters.
08:16
That's about all you're going to get,
08:18
because you can't use the usual sort of systems.
08:20
You can't manipulate it very well,
08:24
although I'll show something about that in a moment.
08:26
So, you take the drop of blood, no further manipulations,
08:28
you put it on a little device,
08:31
the device filters out the blood cells, lets the serum go through,
08:33
and you get a series of colors
08:37
down in the bottom there.
08:39
And the colors indicate "disease" or "normal."
08:41
But even that's complicated,
08:45
because to you, to me, colors might indicate "normal,"
08:47
but, after all, we're all suffering from
08:51
probably an excess of education.
08:53
What you do about something which requires
08:56
quantitative analysis?
08:58
And so the solution that we and many other people
09:00
are thinking about there,
09:03
and at this point there is a dramatic flourish,
09:05
and out comes the universal solution to everything these days,
09:07
which is a cell phone. In this particular case, a camera phone.
09:10
They're everywhere, six billion a month in India.
09:13
And the idea is that what one does,
09:18
is to take the device,
09:21
you dip it, you develop the color,
09:23
you take a picture, the picture goes to a central laboratory.
09:26
You don't have to send out a doctor,
09:29
you send out somebody who can just take the sample,
09:31
and in the clinic either a doctor, or ideally a computer
09:34
in this case, does the analysis.
09:37
Turns out to work actually quite well, particularly when your
09:39
color printer has printed the color bars
09:41
that indicate how things work.
09:43
So, my view of the health care worker of the future
09:45
is not a doctor,
09:48
but is an 18-year-old, otherwise unemployed,
09:50
who has two things: He has a backpack full of these tests,
09:53
and a lancet to occasionally take a blood sample,
09:55
and an AK-47.
09:58
And these are the things that get him through his day.
10:00
There's another very interesting connection here,
10:05
and that is that what one wants to do
10:07
is to pass through useful information
10:09
over what is generally a pretty awful telephone system.
10:12
It turns out there's an enormous amount of information
10:16
already available on that subject, which is the Mars rover problem.
10:19
How do you get back an accurate view of the color on Mars
10:22
if you have a really terrible bandwidth to do it with?
10:26
And the answer is not complicated
10:30
but it's one which I don't want to go through here,
10:32
other than to say that the communication systems
10:34
for doing this are really pretty well understood.
10:37
Also, a fact which you may not know
10:39
is that the compute capability of this thing
10:42
is not so different from the compute capability
10:45
of your desktop computer.
10:47
This is a fantastic device which is only beginning to be tapped.
10:49
I don't know whether the idea of one computer, one child
10:52
makes any sense. Here's the computer of the future,
10:56
because this screen is already there and they're ubiquitous.
10:59
All right now let me show you just a little bit about advanced devices.
11:04
And we'll start by posing a little problem.
11:06
What you see here is another centimeter-sized device,
11:09
and the different colors are different colors of dye.
11:12
And you notice something which might strike you as
11:16
a little bit interesting,
11:18
which is the yellow seems to disappear,
11:20
get through the blue, and then get through the red.
11:23
How does that happen? How do you make something flow through something?
11:26
And, of course the answer is, "You don't."
11:29
You make it flow under and over.
11:31
But now the question is: How do you make it flow
11:33
under and over in a piece of paper?
11:35
The answer is that what you do,
11:38
and the details are not terribly important here,
11:41
is to make something more elaborate:
11:44
You take several different layers of paper,
11:46
each one containing its own little fluid system,
11:48
and you separate them by pieces of,
11:51
literally, double-sided carpet tape,
11:53
the stuff you use to stick the carpets onto the floor.
11:56
And the fluid will flow from one layer into the next.
11:59
It distributes itself, flows through further holes,
12:02
distributes itself.
12:05
And what you see, at the lower right-hand side there,
12:07
is a sample in which a single sample
12:10
of blood has been put on the top,
12:12
and it has gone through and distributed itself
12:15
into these 16 holes on the bottom,
12:18
in a piece of paper -- basically it looks like a chip,
12:21
two pieces of paper thick.
12:23
And in this particular case we were just interested in
12:26
the replicability of that.
12:28
But that is, in principle, the way you solve
12:30
the "fever of unexplained origin" problem,
12:32
because each one of those spots then becomes
12:34
a test for a particular set of markers
12:36
of disease,
12:39
and this will work in due course.
12:41
Here is an example of a slightly more complicated device.
12:43
There's the chip.
12:46
You dip in a corner. The fluid goes into the center.
12:48
It distributes itself out into these various
12:50
wells or holes, and turns color,
12:53
and all done with paper and carpet tape.
12:55
So, I think it's as low-cost
12:58
as we're likely to be able to come up and make things.
13:00
Now, I have one last, two last little stories
13:04
to tell you, in finishing off this business.
13:07
This is one: One of the things that one does occasionally
13:10
need to do is to separate blood cells from serum.
13:13
And the question was,
13:16
here we do it by taking a sample,
13:19
we put it in a centrifuge,
13:21
we spin it, and you get blood cells out. Terrific.
13:24
What happens if you don't have an electricity,
13:28
and a centrifuge, and whatever?
13:30
And we thought for a while of how you might do this
13:32
and the way, in fact, you do it is what's shown here.
13:35
You get an eggbeater,
13:37
which is everywhere, and you saw off a blade,
13:39
and then you take tubing,
13:42
and you stick it on that. You put the blood in, you spin it --
13:44
somebody sits there and spins it.
13:46
It works really, really well.
13:48
And we sat down, we did the physics of eggbeaters
13:50
and self-aligning tubes and all the rest of that kind of thing,
13:52
sent it off to a journal.
13:55
We were very proud of this, particularly the title,
13:57
which was "Eggbeater as Centrifuge."
13:59
(Laughter)
14:01
And we sent it off, and by return mail it came back.
14:02
I called up the editor and I said,
14:05
"What's going on? How is this possible?"
14:07
The editor said, with enormous disdain,
14:09
"I read this.
14:12
And we're not going to publish it, because we only
14:14
publish science."
14:16
And it's an important issue
14:18
because it means that we have to,
14:20
as a society,
14:22
think about what we value.
14:24
And if it's just papers and phys. rev. letters,
14:26
we've got a problem.
14:28
Here is another example of something which is --
14:31
this is a little spectrophotometer.
14:34
It measures the absorption of light in a sample
14:36
The neat thing about this is, you have light source that flickers
14:39
on and off at about 1,000 hertz,
14:42
another light source that detects that light at 1,000 hertz,
14:44
and so you can run this system in broad daylight.
14:48
It performs about equivalently
14:51
to a system that's in the order of
14:53
100,000 dollars.
14:56
It costs 50 dollars. We can probably make it for 50 cents,
14:58
if we put our mind to it.
15:01
Why doesn't somebody do it? And the answer is,
15:03
"How do you make a profit in a capitalist system, doing that?"
15:05
Interesting problem.
15:09
So, let me finish by saying
15:12
that we've thought about this as a kind of engineering problem.
15:14
And we've asked: What is the scientific unifying idea here?
15:18
And we've decided that we should think about this
15:24
not so much in terms of cost,
15:25
but in terms of simplicity.
15:27
Simplicity is a neat word. And you've got to think about
15:29
what simplicity means.
15:31
I know what it is but I don't actually know what it means.
15:33
So, I actually was interested enough in this to put together
15:37
several groups of people.
15:39
And the most recent involved a couple of people at MIT,
15:43
one of them being an exceptionally bright kid
15:46
who is one of the very few people I would think of
15:48
who's an authentic genius.
15:50
We all struggled for an entire day to think about simplicity.
15:52
And I want to give you the answer of this
15:56
deep scientific thought.
15:58
(Laughter)
16:01
So, in a sense, you get what you pay for.
16:04
Thank you very much.
16:07
(Laughter)
16:09

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About the Speaker:

George Whitesides - Chemist
In his legendary career in chemistry, George Whitesides has been a pioneer in microfabrication and nanoscale self-assembly. Now, he's fabbing a diagnostic lab on a chip.

Why you should listen

Someday Harvard chemistry professor George Whitesides will take the time to look back on the 950 scientific articles he's coauthored, the dozen companies he's co-founded or the 50-plus patents on which he's named. (He works in four main areas: biochemistry, materials science, catalysis and physical organic chemistry.) In the meantime, he's trying to invent a future where medical diagnosis can be done by anyone for little or no cost. He's co-founded a nonprofit called Diagnostics for All that aims to provide dirt-cheap diagnostic devices, to provide healthcare in a world where cost is everything.

Among his solutions is a low-cost "lab-on-a-chip," made of paper and carpet tape. The paper wicks bodily fluids -- urine, for example -- and turns color to provide diagnostic information, such as how much glucose or protein is present. His goal is to distribute these simple paper diagnostic systems to developing countries, where people with basic training can administer tests and send results to distant doctors via cameraphone.

More profile about the speaker
George Whitesides | Speaker | TED.com