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Lecture Notes for 10.491February 9, 2001
Soft Lithography
Rebecca Jackman([email protected])
SOF
T L
ITH
OG
RA
PHY
1 µ
m
100
µm 100
µm
50 µ
m
2.5
mm
1 m
m
Mic
rofl
uid
ic S
yste
ms
Gen
eChi
p (A
ffym
etrix
)
mic
ro to
tal a
naly
sis
syst
ems
(µTA
S)
high
-thr
ough
put c
hem
ical
scr
eeni
ngbi
olog
ical
ass
ays
chem
ical
/bio
logi
cal w
arfa
re d
etec
tion
poin
t-of
-car
e te
stin
gch
emic
al s
ynth
esis
Lab-
on-a
-chi
p (C
alip
er)
Har
rison
(U
. A
lber
ta)
Ad
van
tag
es o
f M
icro
flu
idic
Sys
tem
s
•sm
alle
r vo
lum
es -
-le
ss
reag
ent/s
ampl
e co
nsum
ptio
n•
shor
ter
anal
ysis
tim
e•
incr
ease
d th
roug
hput
--
para
llel
anal
ysis
•
incr
ease
d au
tom
atio
n•
impr
oved
inte
grat
ion
of s
ampl
e st
eps
•ea
sier
fabr
icat
ion
Wh
y n
ot
Sili
con
?
•fa
bric
atio
n re
quire
s re
gula
r ac
cess
to a
clea
nroo
m
•pr
oces
sing
cos
ts c
an b
e hi
gh a
nd c
ycle
tim
es lo
ng
•lim
ited
rang
e of
mat
eria
ls c
an b
e pa
ttern
ed
•on
ly p
lana
r st
ruct
ures
form
ed
•ch
emic
al c
ompa
tibili
ty, p
hysi
cal a
nd o
ptic
al p
rope
rtie
s ca
n be
pro
blem
atic
for
som
e ap
plic
atio
ns
mic
ro tu
rbin
e en
gine
(M
IT)
mul
tipha
se m
icro
reac
tor (
Lose
y)
Fab
rica
tio
n in
Gla
ss
glas
s
phot
ores
ist
(1 -
2 m
icro
ns)
mas
k
glas
s w
afer
coat
waf
er w
ith p
hoto
resi
st
phot
olith
ogra
phy;
dep
osit
Cr;
lif
t-of
f met
al
etch
gla
ss to
form
cha
nnel
anod
ical
lybo
nd w
afer
to s
econ
d w
afer
Cr
(100
nm
)(S
ourc
e: M
icro
lyne
)
•co
mpa
tible
with
sili
con
fabr
icat
ion
•tra
nspa
rent
•
insu
latin
g•
low
aut
oflu
ores
cenc
e•
chea
per t
han
Si (
?)
•am
orph
ous
mat
eria
l•
inco
mpa
tible
with
hig
h T
Fab
rica
tio
n in
Pla
stic
s...
•is
che
ap!
•do
esn’
t req
uire
rout
ine
acce
ss to
cle
anro
om•
enab
les
sing
le u
se, d
ispo
sabl
e de
vice
s•
is p
erfo
rmed
in b
atch
but..
.ca
n ha
ve p
robl
ems
with
dim
ensi
onal
sta
bilit
yso
me
auto
fluor
esce
Mic
ropa
ttern
ed b
y:
•in
ject
ion
mol
ding
•em
boss
ing
•m
oldi
ng•
(lith
ogra
phy)
5 m
m
Em
bo
ssin
g M
icro
flu
idic
Sys
tem
s
PDMS-Based Microfluidic Channels
Courtesy of P. Kenis
Polydimethylsiloxane (PDMS) --A Moldable Elastomer
Propertiesmoldabledeformablechemically
unreactivehydrophobictransparent in uv-visinsulating
Applicationssealantsadhesivesprotective
coatings
biomedical useselectrical pottingmicrofluidics /
microchemicalreactors
CH3 Si O Si O CH3
CH3 CH3
Si
CH3
CH3 CH3CH3
( )n
Mol
ding
Pla
stic
s --
Sof
t Lit
hogr
aphy
Siph
otor
esis
tsi
licon
waf
er
phot
olith
ogra
phy
or a
dvan
ced
litho
grap
hic
tech
niqu
e
cast
PD
MS
(ela
stom
er)
rem
ove
elas
tom
er fr
omm
aste
r
Si"m
aste
r"
Si
PDM
S
elas
tom
eric
ele
men
t
near
-fie
ld p
hase
shi
ft li
thog
raph
y
repl
ica
mol
ding
mic
roco
ntac
t pri
ntin
gm
icro
mol
ding
in c
apill
arie
s
mic
rotr
ansf
er m
oldi
ng
PDM
S
“dry
” pa
ttern
ing
mic
rore
acto
rsy
stem
s Kum
ar, B
iebu
yck
and
Whi
tesi
des,
Lan
gmui
r, 1
0, 1
498
(199
4).
Xia
and
Whi
tesi
des,
Ang
ew. C
hem
. Int
. Ed.
Eng
l., 3
7, 5
50 (
1998
).Ja
ckm
an a
nd W
hite
side
s, C
HE
MTE
CH
, 29,
18
(199
9).
Rapid Prototyping
Create designin a CAD program
Print design on highresolution transparency
Use transparency tocreate photolithographicmaster
200 µm
Qin, Xia and Whitesides, Adv. Mater., 8, 917 (1996).
SU-8 Resist -- An Alternative to DRIE?
250 µm
• negative resist• aspect ratios ~15:1• thickness > 700 microns• line width > 25 microns (with R.P.)
Fabrication of MicrofluidicComponents by Replica Molding
replica
flat
Oxidize PDMSreplica and flat inplasma to seal
Remove PDMSreplica from master
Cast prepolymerand cure
Place posts onmaster to definereservoirs200 µm
Duffy, McDonald, Schueller and Whitesides, Anal. Chem., 70, 4974 (1998).
Irre
vers
ible
Sea
ling
of P
oly
dim
eth
ylsi
loxa
ne
(PD
MS
)
plas
ma
oxid
atio
n(~
1 m
in)
air
(~ 1
0 m
in)
cont
act P
DM
Ssu
rfac
esirr
ever
sibl
e se
al:
form
atio
n of
cova
lent
bon
ds
•PD
MS
sea
ls to
itse
lf, g
lass
, sili
con,
sili
con
nitri
de, L
DP
E, P
S
•PD
MS
sea
ls a
fter e
xpos
ure
to p
lasm
a of
air,
dry
air
or o
xyge
n
Rap
id P
roto
typ
ing
of
Mic
rofl
uid
ic S
yste
ms
in P
DM
S
Mas
ter
Tra
nspa
renc
y M
ask
CA
D F
ile
Mol
d w
ith C
hann
els
Mic
roflu
idic
Dev
ice
Idea 24
hour
s
phot
olith
ogra
phy
high
res
olut
ion
prin
ting
(508
0 dp
i)1.
alig
n2.
sea
l
com
pute
r
repl
ica
mol
ding
SU
-8 p
hoto
resi
st(1
0-50
0 ?m
)
Image: Felice Frenkel
Laminar Flow in Microfluidic Channels
l = diameter channel (m)v = flow velocity (m/s)??= density (g/m3)? ?= viscosity (Pa.s or kg/m.s)
Re =l.v.ρη ?
?
Fab
rica
tion
Usi
ng
Mu
lti-S
trea
m L
amin
ar F
low
App
ly d
iffer
ent c
hem
istr
ies
from
diff
eren
t str
eam
s
Au
etc
h
wat
er
Ag
X
redu
ctan
t
etch
ed a
rea
At t
he in
terf
ace
of s
trea
ms
Fro
m s
epar
ate
stre
ams
Ag
wire
P.J.
A. K
enis
, R.F
. Ism
agilo
v, G
. M. W
hite
side
s, S
cien
ce, 2
85, 8
3-85
(19
99)
Ag
X
redu
ctan
t
H2O
Au
etch H
2O
H2O
H2O
Au
Dep
osi
t A
g w
ire
Etc
h A
u
100
? m
100
? m
100
? m
cou
nte
rel
ectr
od
e
wo
rkin
gel
ectr
od
e
refe
ren
ceel
ectr
od
e
PD
MS
mol
d pl
aced
on g
lass
slid
e
P.J.
A. K
enis
, R.F
. Ism
agilo
v, G
. M. W
hite
side
s, S
cien
ce, 2
85, 8
3-85
(19
99)
Fab
rica
tio
n o
f an
In-C
han
nel
Th
ree-
Ele
ctro
de
Sys
tem
Ag
cont
act
pad
to A
uco
ntac
tpa
d
to A
uco
ntac
tpa
d
In-C
han
nel
Th
ree-
Ele
ctro
de
Sys
tem
outle
ts
inle
ts
cont
act p
ad fo
rco
unte
r el
ectr
ode
cont
act p
ad fo
rre
fere
nce
ele
ctro
de
cont
act p
ad fo
rw
orki
ng e
lect
rode
Cyc
lic V
olt
amm
etry
:
10pm
ole
Ru(
NH
3)6C
l 3
in 5
nL
of H
2O
pote
ntia
l vs.
Ag/
AgC
l (V
)
40 0 -40
-80 -0
.4-0
.1-0
.3-0
.20.
0-1
20
RuI
I/ R
uIII
How to pump fluids throughMicrofluidic Channels?
+ + + + + + + + + + + +
- - - - - - - - - - - -
+ kV ground
- - - - - - - - - - - -
+ + + + + + + + + + + +
high P low P
V = 0
V = 0
• syringe pump (pressure driven flow)
• applied potential (electro-osmotic flow)
velocity = mobility * electric fieldcharged particles separated based on
mass and charge (electrophoresis)
parabolicprofile
plugflow
Lab
-on
-a-C
hip
Bas
ed o
n C
apill
ary
Ele
ctro
ph
ore
sis
anod
e(+
)ca
thod
e(-
)
mic
roch
anne
l(5
0 m
icro
ns)
rese
rvoi
r
glas
s
cath
ode
(-)
anod
e(+
)
--
--
--
--
--
--
fixed
cha
rge
on g
lass
wal
l
--
--
--
--
--
--
++++
++++
++++
++++
++++
++++
mob
ile io
nsin
sol
utio
n
++++
++++
++++
++++
++++
++++
wal
l of
chan
nel
net f
low
cath
ode
(-)
anod
e(+
)
++
++
++
++
++
++-
--
--
--
--
--
-
++
++
++
++
++
++ -
--
--
--
--
--
-
+-
+-
-0
elec
tro-
osm
osis
elec
troph
ores
is
mol
ecul
es s
epar
ated
on
base
d on
cha
rge
to m
ass
ratio
Cap
illar
y E
lect
rop
ho
resi
s
Sam
ple
Buff
er
Buff
er
Buff
er
1 2
3 4
Typi
cal s
yste
m fo
r CE
:
•ty
pica
l app
lied
field
s: ~
100
->10
00 V
/cm
•in
crea
se p
lug
size
with
dou
ble-
T in
ject
or•
dete
ctio
n ty
pica
lly b
y flu
ores
cenc
e
“rac
etra
ck”
effe
ct --
band
of a
naly
te b
ecom
e sl
oped
aro
und
turn
Sepa
rati
on o
f Cha
rge
Lad
der
of C
arbo
nic
Anh
ydra
se
PDM
S C
E-ch
ipB
eckm
an C
E s
pect
rom
eter
time
(s)
400
500
600
700
800
tim
e x
field
str
engt
h (s
kV
/cm
)
0
5060
7080
90
1020304050
tim
e (s
)10
020
030
0
140
time
x fi
eld
str
eng
th (
s kV
/cm
)
04080120
4060
8010
012
0
D. C
. Duf
fy, J
. C. M
cDon
ald,
O. J
. A. S
chue
ller,
G. M
. Whi
tesi
des,
Ana
l. C
hem
.70,
497
4 (1
998)
.
1 cm
dete
ctio
n(c
onfo
calm
icro
scop
e)in
ject
ion
+ kV
Gnd
Kee
pin
g D
evic
es C
om
pac
t --
Ho
w t
o m
ake
a tu
rn?
how
to k
eep
devi
ces
com
pact
?
B. M
.Pae
gel,
R. A
. Mat
hies
, Ana
l. C
hem
.200
0, A
SA
P a
rticl
e.
Rep
lica
Mol
ding
to fo
rm L
iqui
d P
hase
Rea
ctor
s
PD
MS
PD
MS
PD
MS
Ep
oxy
Ep
oxy
Si r
eact
or
mo
ld
epox
y re
acto
r
PD
MS
mol
d
62 µ
m
66 µ
m
-0.0
02
0.03
8
0.07
8
0.11
8
0.15
8
0.19
8
0.23
8 49
053
057
06
10
650
Wav
elen
gth
(n
m)
Absorbance
0.25
mL
/min
0.1
mL
/min
0.05
mL
/min
0.01
mL
/min
0.00
5 m
L/m
in0.
001
mL
/min
un
mix
ed
Dec
reas
ing
flo
wra
te,
Incr
easi
ng
co
nta
ct t
ime
Inte
grat
ed O
ptic
s fo
r Sig
nal A
cqui
sitio
n
Fib
ero
pti
c lig
ht
sou
rce
Fib
er
op
tic
det
ecto
r
SU
-8:
An
Alt
ern
ativ
e to
Dee
p R
eact
ive
Ion
Etc
hin
g?
•th
ick
laye
rs a
re p
ossi
ble
--up
to a
bout
700
µm
in a
sin
gle
coat
•hi
gh-a
spec
t rat
io (
Bo
nd
ing
wit
h S
U-8
to fo
rm S
eale
d M
icro
chan
nel
s
Si Si
brin
g w
afer
s in
to c
onta
ct a
t ele
vate
d T
; bl
anke
t exp
ose
resi
st th
roug
h py
rex;
pos
t-ba
ke
if ne
cess
ary,
dis
solv
e re
leas
e la
yer
or p
erfo
rmfa
bric
atio
n on
sur
face
hav
ing
poor
adh
esio
n
coat
tran
spar
ent s
ubst
rate
with
laye
rof
SU
-8; p
artia
lly p
re-b
ake
laye
r
pyre
x
expo
sed
SU
-8un
expo
sed
SU
-8
use
SU
-8 it
self
as in
terla
yer
for
bond
ing
full
waf
ers
all S
U-8
str
uctu
re (
supp
orte
d on
pyr
ex)
pyre
x
Bo
nd
ing
wit
h S
U-8
to fo
rm S
eale
d M
icro
chan
nel
s
•mai
ntai
ns d
imen
sion
s an
d in
tegr
ity o
f mul
tilay
ered
stru
ctur
e
•int
erfa
ce b
etw
een
bond
ed
laye
rs is
not
app
aren
t
pyre
x
bond
ing
laye
r
2nd
laye
r
1st l
ayer
silic
on50
µm
bond
ing
laye
r
silic
on tr
ench
form
ed b
y D
RIE
100
µm
pyre
x
•SU
-8 w
ill b
ond
othe
r m
ater
ials
--
requ
ires
one
uv-t
rans
pare
nt la
yer
for
expo
sure
ste
p
•exa
ct p
rofil
e of
res
ultin
g ch
anne
l dep
ends
on
bond
ing
cond
ition
s
SU
-8 B
ased
Mic
rore
acto
rs
•pr
oduc
ed a
ll S
U-8
mic
rom
ixer
with
min
imum
feat
ure
size
~ 5
0 µm
•de
mon
stra
ted
chan
nels
are
sea
led
and
fluid
flow
is p
ossi
ble
solu
tion
of p
heno
l red
flow
ing
in c
hann
els
200
µm50
µm
cros
s-se
ctio
ns th
roug
hm
icro
chan
nels
5 m
m
Photograph by Scott Brittain
2 m
man
ode
500
µm
50 µ
m
cath
ode c
atho
de p
rodu
ct
anod
e pr
oduc
t
Hyb
rid
Mic
rore
acto
r D
evic
es f
or
Ele
ctro
chem
istr
y
50 µ
m10
0 µm
•el
ectr
oche
mis
try
prov
ides
dire
ct c
ontr
olof
che
mic
al re
actio
n th
roug
h ap
plie
d vo
ltage
•di
men
sion
sof
mic
roflu
idic
chan
nels
can
be
on th
e sa
me
orde
r as
diff
usio
n le
ngth
s•
high
sur
face
-to-
volu
me
ratio
max
imiz
es a
rea
of e
lect
rode
ava
ilabl
e fo
r re
actio
n•
anod
ic o
xida
tions
are
reas
onab
le c
andi
date
s fo
r m
odel
rea
ctio
ns
pyre
x
SU
-8
silic
on
pyre
x
SU
-8
silic
on
Som
e M
ater
ials
rigi
d
fabr
icat
ion
optic
al
etch
ing
etch
ing
mol
ding
tran
spar
ent
opaq
ue
lase
r cut
ting
Silic
onG
lass
Myl
arPD
MS
tran
spar
ent
tran
spar
ent
stru
ctur
eri
gid
‘rig
id’
elas
tom
eric
bond
ing
self-
seal
ing
ther
mal
ther
mal
anod
ic
perm
eabi
lity
--
-or
gani
cs, g
asse
s
Mat
eria
l of c
hoic
e de
pend
s on
:
•A
pplic
atio
n
•P
roto
typi
ng v
s. M
ass
prod
ucti
on
pum
ping
pres
sure
pres
sure
EO
FE
OF
Cou
rtes
y of
P. K
enis