Okay, let's get this
the show started here. So this leads to be very interactive
I'm not gonna stand behind the podium and
I want you to stop me and ask questions we're gonna pass stuff around
And if we get to that we might even do a chemistry reaction
try to make it is as fun for you guys as it is for me
I love to give these kinds of talks because
first of all, if I make a technical mistake you're less likely to see it
and it's a lot of fun to get to talk to people about the work that we do
and get some
fresh input and feedback from people that I don't work with all the time
I will say one thing working at NIST, people leave feet first.
We have a tremendous tenure. If you stay
more than five years at NIST, eighty percent of those people retire from NIST.
So clearly, there's people walking around 90,
95 years old, still coming into work every day. Actually one guy got
his eighty-year pin.
Eighty years. Okay, so first of all I have to say this cause if this
gets out to the public, I have to say that at say that I'm not endorsing anybody.
Anything I say is not the official opinion at the Department of Commerce or
the National Institute of Standards and Technology. It's strictly me telling you my
professional opinion.
And any commercial things that I mention I'm not saying they're better or worse
or good or bad or
they're just aren't telling you what they are.
get my clickers I don't have to go back and forth okay so for those of you that
don't know about missed
om about a nice little place where
all geese are strong all that you're good-looking
Anna all the scientists are above average I am
I wrote this talk on a Sunday listening to NPR's on so we have our first Nobel
Prizes by Bill Phillips
on 1997 on 2001
got another Nobel Prize to eric cornell I'll
then we had John Hall in 2005 and then finding that day
Winland just a couple years ago these guys all work in a
optical trapping so they shine lasers through things and
make adams' Ste stay really really still which make them really really cold
so they make the call the stuff in the universe some the temperatures they're
able to reach her you know submental calvin's
so that the billion degree above absolute zero yes
actually each one of them the first time I met
met Bill Phillips I didn't know he was the inner hey white
the bill I bill and why it and then he's I was at a seminar in and started asking
all these really intelligent questions as I
guys really sharp and so than after the talk
I where they're nice eyes bad I was like up that bill
think but no pretense
you know just normal guy I'll
so we say that this is our half Nobel laureate because I
he's not in this staff person but the research that he did
that got him the Nobel Prize he did at NIST he's an Israeli citizen and
missed cannot hire non US citizens he was here on a sabbatical in
return the University tel aviv and then we have a
John Kane got the Kyoto prize which is like the Nobel Prize in material science
so very prestigious prize I'm so this just a few examples a
the like big names you can find NIST so I'm gonna do a little
personal anecdotal vignette about
what has happened in four generations so from my grandfather
to my father to me I don't have any kids sole use by
nephews as sir that om
so much for my brother grandfather's born in 1925
and a the calculators that they had were these
its common at E eight er and it was actually used
primarily to calculate financial transactions and England
back when they're on the pound sterling pants this crazy
them I don't even know how they
calculate the prices be way this was a given that do it is kinda cool
in that com one side you do addition
and then you could turn it over on the other side you could do subtraction
so it's almost kinda like you know these iPhone
term one way the other way different functionalities so kinda cool
and then this one was a the kurta art
kinda looks like a paper mill I'm so you would slide in your numbers and then you
would crank it in this mechanical apparatus with spit out a number
arm in so in you could buy that in 1948 after
after world war two had finished up and in today's dollars it was 250 bucks
so not not a cheap think now you get a calculator for
free om see
okay so my dad was born in 1951 arm
and he's you slide rule
was in schools in the nineties a slide rule I don't
up but maybe I should
arm and so when he graduated from college my grandparents about him
this calculator a in today's dollars about 150 bucks
not terribly expensive but not terribly cheap either I
and I remember run on a nine volt battery
plug it into the wall and I I would play with it when I was a kid
and get scolded because it was like pride and joy
arm now so I was born in 1975
I've never used in chemical calculator I'd would know what the hell to do with
a slide rule
om and when I was in high school I used a TI 85 so this is one of these first
graphing calculators
and so then if we go to Mike
nephews born in 1996 a
he doesn't think he thinks things that have buttons
are weird so he's not used to anything a keyboard okay
but even that he prefers to type on an iPad than an actual keep
or like that but some have a touchscreen arm
and so anybody have kids around that age
do you know what they call the whole
phone phones in hand-held phones
it's ok it's maybe a little bit non-pc
arm so they call phones with buttons are
how much phones up
um actually my boss has an Amish phone
any teases me cuz is cuz he's like you have to trade your iPhone every day
I can charge my phone once a week as I
well you know you can only make phone calls with you years I can do anything
with mine is like it's not them is a shin problem
do you want battery life for you our performance
om okay so
I'm gonna draw apparel I'm gonna try to tell the story
about how electronics developed I
over the since you know the past 50 years or so
because it's really pretty phenomenal what we can do now compared to what we
could do
I when my grandfather was my age
om and so the in 1965
the cofounder Intel Corporation word more
still around proposed what is known as a
Moore's Law and that is every two years the computing power available
doubles om and so if we look at a at a chart
love the development computing power as a function
my pointer here
com being we can see back here in nineteen hundred we had these the
mechanical coupling calculators that were able to do
you know us calculation every five or six seconds
and then as we move up now the the processes that are currently available
they were able to do
ramp in the 11 calculations per second and so we're actually getting close to
computers now that have the same at least in theory
computational capability now arm and then
he'll hook is on a log scale here on
we get here we're looking at the human brain now
p.m. 1 comment about Moore's Law there's debate
on how long continue because right now most processors
are fabricated on what's called the 21 enemy to process
so that means it's able to make features that are 21 many meters
so that's you took a meter
which is about a yard you cut it up into a billion pieces
YouTube 21 those really really really tiny
and the issue now is the very very
limited by the purity
what you're making because if you think about it 21 animators you're looking at
a few hundred Adams so if you get one Adam that's not the right
Adam in there it a big effect on your system so
while will be able to make things things
smaller it's going to become much much more expensive so they think we may be
plateauing
now that doesn't mean that Moore's Law School point stop necessarily
what we need is some new
algorithm for computing some new platforms a rather than using
transistors using
up quantum
computing optical computing on this is what a lot of the
nobel laureates focus on is trapped in these items so that they get into
particular quantum state that they can control and so rather than operating
with binary transistors either on or off
you can have up to eight different quantum state so that computing power
geometrically
com okay so that this is this is a fun flight
fun cells lights up so I checked on Amazon the other day
and leave here to 128 gig flash drive I
for 14 bucks and
just so you guys can look at like this is one of these kinda disassembled
you can see that the chip ears on this side pass that around
on that was not a 128 gig that's
otherwise I wouldn't give it to you om doing it that for
1390 40 bucks om
which is incredible but if we wanted to build something like this in nineteen
forty
use in nineteen forties star om
we need 1.1 trillion vacuum tubes
and so what is it even wanna back into this okay so these things
are still in use and from the folks at NIS that our analog guys still talk
about how
digital electronics are crap and that the vacuum tubes are still the best way
to go for letting so it looks kinda like a light bulb
and basically it does functionally the same thing as a transistor but it takes
a lot more power
om it doesn't switch not able to switch States
as quickly om in his big big
I'm so we can pass that around look at
they're not all that big a more typical sizes like
you know maybe like that or so but this one is nice because you can see all the
innards
parts okay so we would need
thats by the way that about 150 vacuum tubes
for each person recognized
face
that means a
basically population the world by by just put it in perspective
up we need tuna a thousand square miles
which is roughly about the side the state of Delaware we did 4.7 trillion
dollars
to power I'll these vacuum tubes thats
using the price in just inflation adjusted to the price vacuum tube in
nineteen forties inflation-adjusted now om
which is roughly the US military budget for six years at least that's what
on the records I know some people talk about whether or not that's
accurate
we need 76.8 gigawatts of power
and put that in perspective arm that's about
the power consumption country of Germany so
it would never happen but just to put that
in a little bit more perspective I we could fit
the state of Delaware and Jolly Rancher
about how big that om
we had fun the US military for six years for the price of a bucket of chicken
om and power the country in Germany with
about three AA batteries so
that is a really really mindboggling shift
and that's why these things would be completely unfathomable
somebody in the nineteen forties okay some
let me jump out of the clouds now because thats not an entirely fair
comparison
but at least mathematically it's legit so what caused this
it was a a series of disruptive technologies
so somebody was doing something with pulleys and levers
to do mathematical calculations and they moved along
belong to move along and somebody said I got a new idea
and totally changed the game and what
were able to do so
before 1940 the only switches we have were mechanical relays
basically this is an electromagnet you apply power to the electromagnet
move the peace the middle to one side and close the switch
you turn off the electromagnet the peace medal moves away from them
other peace medal in opens the switch um
their big they generate a lot of heat arm
they have moving parts moving parts are bad om
a lot of electricity they switch slowly
you get energized that magnet in the end physically moved the lever over
and then when you turn it off you have to de-energized the magnet
and then have a spring that pushes it back over um
short half-life could you get a moving part eventually that movie part wears
out
as it slammed up against the other part
many times on its really difficult to integrate with other parts
so the first a disruptive technology
we had was back into which is going around here
so we got rid of the the moving parts
and we because there's no moving parts as a much longer life much lower failure
rate
and actually there's these back into
in the nineteen forties that are still chugging along om
and mother wanna actually the guy the game back into
back into the fishing out was telling me and I don't know if this is true
on that because if their pristine switch inability
that on nuclear subs they still use
vacuum tubes to verify
QR codes to come in to verify the lot authorize a launch
I don't know if it's true been on an
name the celeb it's probably classified anyway om
so in the nineteen seventies
a we started to
we invented the trend well in 1953 Bell Laboratories and into the transistor in
about nineteen sixty became something the
commercially by and we started to get
om integrated circuits and so now we've Jenner
we removed no longer a big things actually
small let me pass one around actually on
my the box
this is an old AMD chip
I don't remember it's an apple on
when I bought it was probably you know state-of-the-art now it's worth
nothing I'll let me just point out so this little silver part you see here
that's the that's actually the
the meat the computer part it's about the size of a thumbnail
and then on the other side we have all these pens allow the electronics to go
into now
so the actual chip itself as the small thing all those others
just interfaces the microscopic world arm
so if we if we if we make a parallel and we say a computer
that existed on in the night
like around the time the eniac so in the nineteen fifties or so we said that
its speed was equivalent to them how fast a snail could move on today's
computers
would operate at a speed that roughly quarter-million
times faster in the spatial upon reentry into her
and I didn't do the exact calculation but that might actually be violating
I'm standing in speed of light I think but
will forgo that on
okay now I wanna say down to because on
if I break it will kill me
I'm EU's chemistry and biology interchangeably now om
you know there's an kind of a joke going around at one point it said
when I started college I learned that physics was math chemistry with physics
and biology was chemistry com
mmm sunny use these things can be interchangeable E
especially because we're operating at the interface
read at the junction between what one would traditionally called biology
and one which traditionally call chemistry com
so here on the left is a picture
chemistry lab at Harvard in 1902 and then on the right is a
chemistry lab at the University of South Carolina in 2006
if you hadn't looked in my lab in 2014
it would look roughly the same is this in that
we've got dude standing around beakers in test tubes mixing things
in 2006 we still have we've got one big change
we now have a dude and a girl om
actually where I work at this now we're more
more female than male is about 55 percent female
45 percent male om back in the seventies we have a picture
other auditorium at NIST somebody giving a talk and it said a
missed Diversity Committee sign in to see
it's about 200 people all in black suits with a black tie
and then one guy white blazer not a girl to be seen
com hennen even its
this is unpalatable in today's world
but om in this is kinda the more that I liked propagate
in the sixties
fifties and sixties there actually was and miss
in BS contest and so there was Miss
physics and miss chemistry and
this electronics and I don't know and they actually have like
fascism beauty contests and just
I can't even fathom having even
that can even be bada in today's world but
in anyway still operating in the same paradigm we haven't had this big shift
from you know being able to fit
basically all these books in this library on a little devices by the
grocery store
arm so what can we learn here
is have to merge into the stalking
wondered if I'm on the right one I'll you
so Electronix are nothing more than the interactions of electrons with various
components
and then computers are basically
sophisticated machines that allow the controller
where electrons are movin and how fast they're movin and how many of them are
moving in which directions there moving
and that allows us to do some really amazing results to process
information
so chemistry really is just nothing more than the interaction
different molecules with each other okay so we control where molecules move
if they're allowed to mix or we separate them or
we get them ha cold these different things
om so can we make something analogous to this
that would produce sophisticated machine that allows to learn about chemistry and
biology
or also this will be the last little bit actually use these machines
to do chemistry to make things okay
so I realize this is a broad audience
so this is gonna be maybe a little bit elementary to some folks and maybe two
other folks
it'll be a reminder
high school biology classes I'm so DNA is the blueprint
%uh life 0 sorry back a say one thing
I'm gonna draw a parallel how DNA sequencing technologies developed
from when I was born in 1975 until
today and just how much has changed
in those almost four years forty years yet for years
com
okay so DNA is the blueprint applied informational molecule it's what
make me not have hair and
that back there before haired me
arm in its up
it's made out of four letters mainly there's there's
a courses exceptions and modifications but we have
a the first one is at meaner with related a
the structures will be on the quiz later I had to memorize them when I was in
undergrads you know there the other one is tiny
related with T a then we have one
abbreviated G and then we have a cited seen
abbreviated with see and what
should jump out at you is that the yellow and the blue
kinda looks similar right and the pink
in the green kinda looks similar similar shape
common that's because these two like to get together
and needs to like to get together and that allows us to create double-stranded
DNA
that a little bit
detailed om okay so the order these letters in the DNA
are the instructions so AAA GGG read
GA are two different things so
I could take a some English letters and say
tie your shoes I can take those same letters and rearrange them
and say rally hoist same letters
different order completely different meaning arm
the same thing with DNA you got those four letters but the order
those is exactly critical to what the molecules able to do
by the way this was probably the hardest part
making this of finding something that actually made sense but wasn't
on
lot a four-letter words were able to come okay
so let's look at DNA sequencing
and how did this all get started arm first demonstrated in 1975 by gaining
Frederick Sanger at the University of Cambridge in England
I'm he sequence
gmail by X 174 I X 17
next that it's a virus that attacks E-coli
pretty simple virus and
its its genome is 5400
bases are letters long arm
and so in 1980 he got the nobel prize but was a sec
Nobel Prize his first one in like nineteen fifty-seven when the few people
that has
to Nobel Prizes so what he demonstrated in 1975 was a very laborious
difficult time-consuming
technique in 1977 there were two different methods that were developed
and up until about two thousand and 5 ever so
they were the though biggest workforce technology they're used
in labs when I was in grad school and when I was a postdoc even om
him so walter gilbert who is a professor at Harvard
up published his method in the preceding the National Academies of Science
in February 1977 and then
Frederick Sanger published and updated method on
in December 1977 so you know you like
in the scientific world in you you publish a paper just
a few months after somebody published a similar paper and they're both really
good we call it getting scooped
and it really really sucks as you can imagine these guys were
three or four years on this project and somebody beat you to the finish line
actually here is not the word
is
but they both got the nobel prize in nineteen eighties so Frederick Sanger
passed away
about a year ago walter gilbert running around okay
so I'm gonna try to explain in simple we're gonna sequence a PC DNA
very short pieces DNA again trying to come up with the word with only four
letters
said Gaga gagged her princes Lady Gaga
make it you guys really meat dress
crazy girl
okay p.m. in what we're gonna do is we're gonna make a bunch of copies
that remix four sets of copies oneself cop
one copy set is only get consist
a pieces that in day so we have GA GA GA
you did on the really create another set
only ins and tease we basically
read out the pieces DNA to reality and then we stop
and we do the same thing for the Seas and again the same thing for the G's
now arm
what we're gonna do next is really do a technique called
elector freezes pictures I'm
may be easier and so what that allows us to do is measure the link that the
molecule
and so if we can separate and find out which molecules are short
and longer which one is one base long two bases long
three bases long bases long and we know what the end is we can read out that
letter
so we put that in there we apply electric field in long pieces in DNA
move really really slow
short is DNA moved past and so
if we if you put it in the electric field
yes sorry elector freezes so what we do use DNA
negatively charged at the polly an eye on so
p.m. negatively charged if we apply a positive field here
and negative charge here and we start the DNA me a little but its
will start to move in this direction and
the smaller they are the faster they go these
the median that there and it's called
a gel and it's basically looks like jello
our rooms or poly acrylic my
there's a broader eleven different chemistry but if I were to pass it
around I can't pass it around because a lot of its toxic
om but it would look
feel like jello really stiff jail
like the kinda jealous you need to make George dating
the alcohol doesn't let the jello Chelsea are
anyway we had the G's here
and then we apply the electric field in a movie and based on the size
we know where they are and we can see that each one is in a different place
so evil apply the electric field for a certain amount of time
until they've all separated so this one hears
the biggest piece in DNA and it's in there an RT pop
the letter T not like HD om
so we know that insanity and then our next shortest one
is in our a pocket so you know the ins and a the number three is a C
notin see I number Four's again from our
a pop so we know that that molecule in the day and we keep going keep going
through this om and what we finally see
is that we get Gaga gagged
a cat so it backwards revelry doubt that sequence
arm
okay so in the mid eighties this was done in
a technique called slab gels was a something up
get a picture
must've been really happy image
yeah okay so here's a picture of it it
it's something about the size of a big sheet cake om
you and so you you load your DNA
up here in your ply the electric field in the inning
arm so here's our
challenge list here's its low use radioactive label
we don't like reactivity arm you have to pour these gels by hand so you
you graduate students that makes up the polymer
in a liquid they poured out into the cake pan they let it sit
AP lit up and they put it into another device the load in their DNA samples
they apply the electric field they go home in a sleeper for hours
then they come back into the lab and they look at the jail in the
read out the jail just like I did for you accept these children are really big
and so that's the life of a graduate student
back in the mid-seventies if you're working in DNA sequencing
I so in about 1980 guy named Leroy hood
and is registered in
wordsmith in into the technology that allowed you to do automated DNA
sequencing
so now you can load up your gel look at your DNA
go home and sleep for eight hours and then come back in and get a printout
what your DNA sequences and then you re om
its flow still very slow but we've got rid of the radioactive labels
and the manual preparation and data readout
big step forward com
so in the nineteen actually did my PhD
on capillary electrophoresis I'm so
in the mid nineteen nineties they started doing these things in
capillaries
and so a capillary is nothing more than a really really really skinny to
and so if you can see
arm this right here is the capillary barely visible in this picture
and its taped onto this white plastic piece
with electrical tape ordinary electrical tape action they were
also using something akin to chewing them at one point on
or that sticky stuff used to stick posters on the wall
tacky stuff this is an actual capillary that we
you could use to do DNA electrophoresis I'll just pass that around
you get the feeling that the outside diameters 360 microns which is about
diameter two or three hairs human hairs
in Yuma secure areas the inner diameters about 50 microns
on so that's five won millions
me and you can't see it
in his taped up because ok you you actually cut yourself
pastor
om
so it's relatively slow but not as slow
get rid of this requirement to use a lot of chemistry because
are sorry a large amount stuff cuz instead of pouring out a cake pan
full of stuff you feeling this EB EB BB BD 2
with Stussy just need maybe a teaspoonful materials around
from rather than leaders have material to run once
but the problem is that those
silica capillaries it's made out a quartz actually
com are very sensitive to fouling
and so if you start to get junk on the inside that too
you no longer able to the separation so the in
and the other thing is you notice that that one capillary
so you can only do one sample at a time
with that slab gel you could have many different samples
so I liken it to the capillary electrophoretic the capillary version is
like a Ferrari
will go really really fast but it's going to break down all the time in its
own we'll carry two people
whereas the slab gels are kinda slow
I'm clocking but they work is like an 18-wheeler
you can load it up with a buncha stuff it's only gonna go sixty-five seventy
five miles an hour
but it can bring a lot of stuff with yep
Schur please
well as able to process a lot of samples appease the DNA
different beanie okay sorry
okay a so I'll
when we do DNA sequencing analysis we need to separate
a lot of different DNA samples okay
in the more those that were able to separate the more information really get
so I can separate one sample really fast
or I can separate 32 different samples
really slow but in the end I'm producing the same amount of data per time
okay whatever you want to look at
okay so if we read out
the DNA code we can sequence the genome I
we can tell what kinda phenotype what kind of characteristics that organism
so base you can predict I color hair color
skin color propensity for certain disease types
a lot of stuff
set sacred okay
cool okay so then
when I was in grad school up people started doing the things in
and ninety-six capillary arrays and you know why they chose 96
I cannot member people like to take like 10
101,000 official
that's a good answer pre-budget
om so everybody does their
analysis and what's called a 96-well plate so that means that we're doing
ninety six different pieces of DNA
in a in a standard form factor
and so what that a lot so people in their work in
units 96 you can do you got a sample tray with 96 samples and you do 96
capillaries
you're off to the races arm this is actually a
is an instrument that I had in grad school are called a
Megabass because was able to produce 1,000,000 bases
have DNA informations was able to read out 1,000,000 letters at the DNA code
in one day and we thought we were
that word
arm been and
this guy cost about two hundred fifty thousand dollars back then
you can see the ninety-six capillaries that are dip down into this 96-well
plate with the DNA is
there's an electric field apply the name
all ninety six different pieces DNA moved through that capillary there's an
optical scanner here that the text them
and then ago here in two ways okay
so it still slow but we've gotten rid of the little took
cat sample capacities were able to look at 96 his Indian a rather than just one
are but it's still finicky because now you have ninety-six capillaries all in
one unit
one goes bad then you get ninety five pieces
DNA to go bad 94 and eventually at some point you say well
times what about the arrays that makes the company really happy because they
can sell you these things that
crazy price makes you really sad because you've spent a lot of money
an you have to swap it out do a whole bunch of in
realignment and recalibration readjustment the instrument
but these were the instruments that did the the initial human genome project
so up in Rockville there was a company called elaire
they had hundreds these things running 24/7
arm and then there was Tiger which was the
Institute for genomic research which is the government effort
they had thousands at these things as well p.m.
Applied Biosystems and molecular dynamics for the two companies that made
these instruments
they mail money and they're actually with
in cahoots with other people as well okay to the human genome project started
in about nineteen
ninety and it was an initiative
a put forward by president clinton
to sequence the human genome in its entirety
so the human genome is about 3 billion base is long om
and we wanted to find nobody had done it before so we didn't know what the
library of the human
cold was and so there was a huge initiative the cost
about $13 billion dollar took well over 10 years
on to read out all those three billion bases they sequenced
the genome a single female I
don't know name is Don that one lucky person was the first person to get there
genome sequenced and it cost us like I said 13
billion with be dollars I'll
so in the nineteen nineties in this is what I did my research on is
that we started to move these into microfluidic devices
some gonna pass a couple things around don't give these back to me because
we're gonna do a demo in a little while
and I want you to have at least one you can look at with your neighbor
and I'll explain what these things are
might have to share more you guys don't need to see a
unity is
work in my lap they work in our lives
okay so if you can kinda read your finger on their you can feel some like
group the
on one side unless it's a sealed ships might be sealed
the sealed ones you can kinda feel those
group those groups are actually a the tubes
so what we've done is we rather than make
using one of those glass capillary tubes we've actually made it to
are in this device now what is that gains
there's one big change we go from one-dimensional system
were the only thing we can control is the link that the two
to a two-dimensional system so now we can make things that go
this direction in this direction restrictions now we can start playing
games
about rather than just movin a DNA molecule
in one direction we can start to show that around different directions
and that allows us to start to do a lot of cool stuff and so we started doing
a started doing DNA sequencing
in these devices om it was
it solved all the problems except it was damned expensive
really expensive om because
this old guy here this is a silicon one not the plastic
guess how much is gas to make
we used use the same techniques that you use to make a microchip
so when they make a microchip they fabricated on a wafer thats
a certain diameter and then they cut it up into a million pieces
because they make a million chips on that and the package a month so
when you fabricate and lets a 12-inch wafer
and then you cut it up into I don't know how many chips 12-inch wafer but you're
able to
amortize the cost that chip over all those devices and so you can sell a chip
for a couple a box rather than that so this
actually costs about ten thousand dollars to make old
don't drop it no attorney broken
I'm that's how to use it as a demo and another one
yes so
are so this one's made at uva
material called silicon om
it's this material that computer chips are primarily made out of
on these in order to get around this ten thousand dollar cost we tried to start
making them in plastic so that they were cheap
is plastic cheap this were
you once led her to me I think know you are
okay so this is actually
aversion a the chip that passing around
under a microscope okay and so remember said we were able to start
now that we have a two-dimensional system we can start to move DNA in
different directions because we can make it
intersection tery your whatever you can dream up
so get it shipped out so if you look great here
and who I forgot ship
so
don't no pride no shame I have to use these
so this is just a jeweler's loupe so you can look up
maybe make it a little easier to see they're coming back
arm
actually I was I was with
a in the lab the other day and we were looking at a computer screen
get data and I didn't have my glasses on and I was
and I had to finally zoom the screen and my boss is standing back behind me
and he started make a comment about my eyes
starting to like shot quite om so that's why
jewelers anyway argument
or any so we apply a voltage
sorry we loaded the United the DNA in this case is labeled green
okay and so there's a mixture of DNA in here and we're gonna separate that DNA
we apply a voltage in this direction
so if you look at one edge have the device over here you can kinda see a
a little cross where the where the holes or there's a pension
like 16 holes there we're only looking at but when we look at one of those
lines
not all you love them so we apply this voltage from north to south and then at
a certain time we're going to switch
and we're gonna play the voltage from
weft East and so what's gonna happen is that the DNA that caught
in this little intersection here is gonna start to move
down this direction and so
just so you know a typical DNA sequencing run takes about an hour
to do with the traditional techniques that we've been talking about before
and I'll show you how long it takes to do with this
in ago
good so we switched the voltage right about there
and you can see the DNA moving down there
and here in just a little bit you start to see the different pieces
DNA appear you get these bands third
simply
dard is under a microscope so and and it's a fluorescence microscope and so
lots of things for us dirt is one of those ominous impossible to keep these
things
perfectly clean there's techniques for
getting around that but this has been done in a microscope
actually when I was doing this work
we have the world speed record for DNA sequencing I'll
had it for like three months he yet
yeah I am suspended upper slowdown it some
because the way the microscope operates
arm that's where you get this kinda I'll
holes
yeah frame rates I thank you brain freeze yeah that's because it's taking a
picture
every couple seconds cuz the way it works it takes a while to scan the whole
image
okay so missus have a fun place so I had given this
talk added internal division meeting
and a when these guys he started working at NIST in 1950
ominous would've been in 2002 guys been around for a while
arm name is wolfgang heller
from Austria most famous for creating controlled pore glass
cool om
side presented this in this older gentleman at that point I didn't know
him
your process and he said and I'm gonna paraphrase I'm really glad
you guys are starting to work on this stuff again a
and then he showed me a
this which was at back in nineteen fifties
when he just started working in this was a top-secret
gizmo a pass around be a little bit delicate with this because
it is kinda special to me anyway arm
so what is this gizmo
NIST back then was called National Bureau of Standards
om and it how's the diamond ordinance
laboratory burdine sorry diamond ordinance
fuse laboratory so what if used the its
the I what's a good device that was credited with winning world war two
next to the a bomb and so what it is
is it controls when a bomb explodes used to just drop a bomb and when it hit
something up
then they started putting in these devices that would tell it to blow up
when it reached a certain altitude
or certain velocity or a certain
whatever parameter you wanted to set com they only use them
over water never used them on Lancaster word
one would fail in the germans find it reverse engineer secrets
I and it moved to the Army in 1952
so here's a picture that guy and so what is it
it's actually and analog pneumatic
computer to control the detonation of a bomb a
in the case of a nuclear attack so you not familiar with
if the nuclear bomb goes off you get an electromagnetic pulse
an all-electronic go crazy so this was a backup device
so with than if the russians new us week in New
back om without the effect that the
that kinda that's why it's fun to work at NIST is because you know you show
this
that he really really proud of and some old guy comes and says
we're doing that when your dad was a kid
okay so here's where we are in the first 30 years in DNA sequencing
I 1975 to to sequence 5,000 bases
took more than a year took a world-class you know
Nobel laureate research lab in england
and god knows how much money it cost because
calculate that I'm and then in 2005 using that Megabass we get sequence
a million bases in one day with one technician
for about a thousand dollars so if we take this snail speed analogy now
sequencing in 1975 moved at a snail's pace
in 2005 we're movin at about two times the speed to the camp Concord
this is really really good
but it's also really not good because we're doing the same
ru still doing the basic same thing
but Indian an electric field moving it in separating
by pieces there hasn't been a fundamental change we have gone from a
vacuum to
to integrate circuit or from a mechanical
computing device back into there hasn't been a big while
in till that 2005
so I would say that DNA sequencing
just went through something they can to the introduction of the integrated
circuit
in 1970 in talking about for sir
so we look at this chart this is the log chart the cost
it takes to produce Megabass if DNA sequencing
on here's a pseudo Moore's Law so that means that every two years ago its
price cuts in half and we see that from 2001 to 2005
when we were building these capillaries microchip a systems we were decreasing
the cost
pre/post Moore's Law and then something happens right around here
what happened pretzels and
drops down to nothing om there was a new disruptive technology that came around
and it was the ability to
rather than taking a big group of DNA molecules
in separating them we were able to take a single molecule DNA
interrogated take one molecule DNA
and read its bases 123 456 789 10
that's kinda cool but we were able to do that
take a million pieces a DNA or tens of millions of pieces
DNA and then read each one of their sequence simultaneously
sore reading each individual piece of DNA a million times a million pieces
DNA individually at the same time phenomenal
why are we able to do that how are able to do that I
I would say that's because we're starting to blur did lines between the
biologists in the chemists
in the physicists in the material scientists in the computer scientists
a twenty years ago a biologist in a chemist
different languages just like I'm using a different language I'm trying to do my
best
problems in some language little confusing om
so now arm we can sequence
so we go back to the 1975 analogy and say that's a snail's pace
right now we can produce 3 billion
faces a DNA information in one day with one technician
for 1000 bucks 3 billion base is a DNA is the human genome so
in theory in theory
it's not exactly doable in theory
do that for 1000 bucks today so now ur four times special
every entry not a quarter million times for now
or four times com but you know
five years ago in iPhones every runaround blackberry
look
had no no these are great questions
please ask these questions um
so here's a picture
wanted these actual devices arm I could not get a copy of the video
because it's blockbuster
are there's the functional device
so we go back re:
so here's the actual instrument so it's it's notes like EA buy you a
these folks actually use the inkjet printer model they say the instrument
for free
or almost free but then that the kid you have to use to do they charge at the was
for om won the wasn't
I this one is called an alumina
there's about five different vendors that make them
and they all operate on the same procedure reading out
each based on a single piece of DNA and in doing that on a million pieces
millions pieces a day but the interrogated differently
on them to electronically optically said
enzymatically lot of different ways com
so here's the gizmo the actual device
this is a standard pins you get an idea scale
and what happens is you too high
a buncha pieces of DNA under the surface and
you take a million copies I'm not gonna go into details
do it but you basically take a million copies a single piece of DNA
and you put that in one spot and then you take a million copies of another
piece of DNA
saying the city in a bit then another spot and then you do
you take an enzyme that breeds of the DNA bases and each time it sees a
different DNA bases flashes a different color
so you know when you see a pink flash there was any
you see a purple flash there was a T whatever
and you put a camera on their in what you get
it looks like static on a old TV screen an old-fashioned
calls for two different colors flashing all over the place that's what it looks
like
each one of those pixels as that color changes is telling you what the
sequences on that particular DNA
you can log all that data you feed it into a huge computer
and resemble like the world's biggest chip
really pretty cool
so here's where with them to this phone
this is actually work its and services you know about that day
and you get go and thats
come back in a couple hours you get your
billions bases in DNA information unpalatable
when I was in grad school we were working on this and we would get where
we could make
thousand bases in a couple hours were really rock
and in so many publishers a paper we like
I'm done this technology is
at it and I've been vacuum tube has been replaced
the integrated circuit okay so now this is gonna be maybe a little bit more
different more fun maybe so can we use chemistry To make stuff
use these new chemistry is to make things on
should and so wanna talk about now is something called a liposome
an Olympic was nothing more than an artificial
cell its basically
ok a little man ok container will small-scale container
I made outta
up lipitor see they're like
advertised in alpha hydroxy
therapy in skin creams in this kinda stuff that basic sing and stuff but
what's cool about it
is it's a tiny tiny container and whatever's on the inside
can't get out waters on the outside getting into you
change something so you can open and close them
permeate them but in general these days
okay so the current state-of-the-art involves
are you take the precursor component have a lipid
to get these individual lipid molecules they're completely happy
and you put them into a different solution and they're no longer happy
and they start rather than being individual lipid molecules
they start to Guam up together in the liposomes these
the spherical such
containers if you will the problem with that is when you pour that in
you mix those two fluid there's no way in heck
you can mix this the fluids exactly the same
over and over again when you do it with psych test tubes tied things
just it's just physics aren't there so I'm gonna show you this maybe
I'll see if this works work in my kitchen last night so wanna do isn't
accrued uncontrolled mixing up to solutions
these are non-toxic
pro one of them I know you've eaten young
the soak your feet in so we have a clear solution
and I'm just gonna it without any control
were in my second solution it's gonna make the ions in this solution and happy
and they're gonna do turned Road
and then I'm gonna pass this around
and you can look at
how different the sizes are the chunks in there
are huge different sizes by the way that epson salt and baking soda
so and water
so what you have to do is when you mix the lipids and you get is
crap is John this is that you have to process it to make them all the same
size
because it's critical the same size because when you put them into a person
you want them to be other controlled size in the same size
otherwise well the first were you clog the plumbing
actually in an embolism om
the other thing is that they'll get cleared by the renal filtration system
with the liver or the loans or the spleen depending on the size
they can trigger an immune response they can do all sorts of nasty things
so you get this gizmo here that's a
weighs about 50 kilograms it's about a cubic meter in size
and it will basically force these things through
membranes that cause im size okay so
that process takes couple hours
you have to buy this big box but
is we
mix these two things
in a microfluidic system or in one of these micro chip Systems
were able to do the mixing in a controlled way and do with the same
every so no longer do I have a
jar full a John I haven't whatever's Camino my chip
isn't controlled size and it's all the same size
something to pass this around few jewelers loops are still there that
could be useful
it's gonna look kinda like a while and
1 I'm sure years that he but it's the same basic idea we're going to flow in
are liquid solution flow in another solution that makes the lipid unhappy
and they're going to self-assemble into liposomes
and so schematically what is happening is
were flowing in one fluid in this direction
and we flew in our second fluid in this direction
and they stir to mix it this interface but rather than mixing in the big
splashy
crazy way they're mixing in a very the
nice and so what's the application
to this com let's take
medical imaging so this is a a positron emission tomography or PET scan
a rat with junkie
bad loans something like that and what you see is that
almost all the the radio pro
trying to visualize the rat the inject tracer some kind of a probe into the rap
arm is getting caught up in the liver you can kind of make up
several artery may me something here but
livers lit up like but
if we take those use this some device to make those liposomes
tiny and have controlled size in we support them into the rap
this is my picture by the way
these are my pictures
so now what we can see
on the rats and I we've made the good liposomes and then this was actually
made with
device just like the one that's being passed around so we're able to make this
in basically plug the chip directly into the rat rather than
making this stuff in this big radio pharmacy with
clunky machine
card to the operating room and then the patient so you can see we get very clear
we can see the entered scepter we can see the femoral artery a crowded artery
a get a little bit a kidney uptake we can see it's a boy rap
and then
over a period of about four hours that radio probe starts to dissipate
and it's actually a also yes
uptake surrogates its taken in the bonuses a flow right pro
so the same reason he's fluoride toothpaste attacks
to the bone starting to stick in the bones the rat
and its actually sticking in at the growth plate worst part
ball to your sister to see the skeleton at that point you never do
Askim just do an xray arm
in I know this was a little bit cursory com
but I'm at a time and I think
okay I don't do this stuff myself by myself lot of folks who work with
NIST is a great place really like it they're material laboratory
do a lot of work with University Maryland College Park
the different NIH institutes and I have a a burgeoning but
really growing collaboration with University
unique up in Campinas Brazil which is the biggest universe
one of these universities in Brazil Campinas is about two hours west
all so they in student
and I get to work
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