A methacrylated photoiniferter as a chemical basis for microlithography: Micropatterning based on photografting polymerization

Article abstract of DOI:10.1021/ma0344341

A polymer patterning technology based on photografting polymerization mediated by photoiniferter chemistry is presented as a simple microlithographic technique that affords flexibility in fabricating and subsequently modifying polymer substrates with vari

Full text of DOI:10.1021/ma0344341

Macromolecules 2003, 36, 6739-6745
6739
A Methacrylated Photoiniferter as a Chemical Basis for
Microlithography: Micropatterning Based on Photografting
Polymerization
Nin g Lu o,†, An d r ew T. Metter s,*,†, J . Br ia n Hu tch ison ,†
Ch r istop h er N. Bow m a n ,†,‡ a n d Kr isti S. An seth †,§
Department of Chemical Engineering, University of Colorado, Boulder, Colorado 80309-0424;
School of Dentistry, University of Colorado Health Sciences Center, Denver, Colorado 80262; and
Howard Hughes Medical Institute, University of Colorado, Boulder, Colorado 80309-0424
Received April 4, 2003; Revised Manuscript Received J uly 3, 2003
ABSTRACT: A polymer patterning technology based on photografting polymerization mediated by
photoiniferter chemistry is presented as a simple microlithographic technique that affords flexibility in
fabricating and subsequently modifying polymer substrates with various chemistries. In principle, the
technique relies upon the design and synthesis of a methacrylated photoiniferter, (methacryloyl
ethylenedioxycarbonyl) benzyl N,N-diethyldithiocarbamate (HEMA-E-In). This photoiniferter allows the
production of micropatterned polymer substrates with surface or internally grafted chemical modifications.
The ability to modify surfaces with covalently bound polymer is demonstrated where the thickness of the
layer depends on the exposure time. Furthermore, patterning chemical surface modifications was achieved
by combining this process with photomasks to produce micron-sized features (approximately 20 µm).
The method is quite diverse and enables spatially controlled internal modification of polymer networks
as demonstrated herein. The developed techniques should be very useful for the facile development of
2-D and 3-D patterned and surface-modified polymers for microfluidic and biomaterial applications.
In tr od u ction
assembled monolayers. Scotchford et al. cultured pri-
mary human osteoblasts on carboxylic acid- and methyl-
terminated self-assembled monolayers of alkylthiols on
gold and measured kinetics of cell attachment and
proliferation on these substrates.11 After 24 h the
number of cells attaching to carboxylic acid-terminated
monolayers was 10 times greater than on methyl-
terminated monolayers. The patterns of the carboxylic
acid-functionalized areas also strongly influenced the
morphology of the attached cells.
From a biomaterial perspective, techniques that en-
able facile production of topologically and chemically
controlled regions on the size scale of a cell and greater
are highly desirable, and a basis for many biomaterial
patterning techniques is found in photolithography, a
technique that was originally developed for the semi-
conductor industry. In the method, a silicon oxide
substrate is coated with a thin layer of photoresist and
irradiated with UV light through a mask. The exposed
regions are removed in a developing bath to reveal
complementary patterns of silicon dioxide and photo-
resist. Subsequent immersion of the substrate in a
solution of alkyltrichlorosilane forms siloxane organic
layers. The remaining photoresist is then removed, and
a different siloxane is formed in the complementary
regions. Photolithography readily achieves a spatial
resolution of 0.13-0.15 µm, but the required photolitho-
graphic equipment and a controlled environment facility
make this technique expensive.
During the past decade, the development of micro-
patterned surfaces, especially biomaterial surfaces, has
been extensively explored for applications ranging from
biosensor technology1-3 to tissue engineering4,5 to fun-
damental studies of cell biology.4-7 Specifically, biosen-
sors based on living cells have been explored for
environmental and chemical monitoring,3 and position-
ing and patterning of the cells on these devices are
critical to sensor performance. In tissue engineering
applications, micropatterned surfaces have employed
variations in charge, hydrophilicity and topology to
regulate cell function and create organized structures.
Endothelial cells spread and grow on large (>100 µm
diameter) microcarrier beads,8 whereas they rapidly die
when bound to small (4.5 µm) extracellular-matrix-
coated beads.9 Chen et al. used micropatterned sub-
strates to control the shape of human and bovine
capillary endothelial cells.7 They varied the extent of
cell spreading while keeping the total cell-matrix
contact area constant by culturing cells on substrates
with 20, 5, and 3 µm diameter islands, separated by 40,
10, and 6 µm, respectively. They found that the extent
of spreading (the projected surface area of the cell), and
not the area of the adhesive contact, controlled cell life
and death. Mrksich et al. used microcontact printing to
pattern gold and silver substrates into regions of oligo-
(ethylene glycol) groups and methyl groups.10 After
coating the substrates with fibronectin, bovine capillary
endothelial cells attached only to the methyl-termi-
nated, fibronectin-coated regions of the patterned, self-
Alternatively, microcontact printing, which uses an
elastomeric stamp for pattern transfer, has been widely
reported as a nonphotolithographic micropatterning
technology. As an example, it can conveniently be used
to pattern alkanethiolates on gold surfaces with features
as small as 1 µm.4,12 Spatial resolutions as small as 200
nm can be achieved in special cases.13 The stamp used
in microcontact printing is formed by casting poly-
* Corresponding author.
† Department of Chemical Engineering, University of Colorado.
‡ University of Colorado Health Sciences Center.
§ Howard Hughes Medical Institute, University of Colorado.
Current address: Department of Chemical Engineering,
Clemson University, Clemson, SC 29634-0909.
10.1021/ma0344341 CCC: $25.00 © 2003 American Chemical Society
Published on Web 08/12/2003

6740 Luo et al.
Macromolecules, Vol. 36, No. 18, 2003
(dimethylsiloxane) (PDMS) against an appropriate relief
structure, usually a photolithographically produced
master. The PDMS pattern is then inked with a solution
of alkanethiol in ethanol, dried, and manually brought
into contact with a gold surface. Conformal contact
between the elastomeric stamp and surface and the
rapid reaction of alkanethiols with gold permit the
surface to be patterned over an area several cm2 in size
with edge resolution of the features better than 50 nm.
Because microcontact printing is a technique that does
not require stringent control over the laboratory envi-
ronment, it can produce micron-scale patterns conve-
niently and at a low cost relative to photolithographic
methods. Microcontact printing has also been used to
pattern alkylsiloxanes on the surfaces of SiO2 and glass
and on nonplanar and contoured surfaces.13,14 However,
both photolithography and microcontact printing tech-
nologies share some common disadvantages, such as
lengthy preparatory procedures and low flexibility with
regards to usable surface chemistries. Thus, new mi-
cropatterning technologies are needed, especially for the
biomaterials community, that combine the desirable
features of low cost and simplified operation with wide
compatibility with a variety of polymer substrates.
solutions. In the second method, Nakayama et al. made
highly cross-linked polystyrene films with chloromethy-
late groups.20 The film was subsequently modified by
potassium N,N-diethyldithiocarbamate trihydrate to
attach photoactive dithiocarbamate groups to the sur-
face. Three different polymers were grafted onto the
same substrate surface using this technique. Cross-
linking of the films was necessary to allow the use of
organic solvents in the sequential modification proce-
dures.
Matsuda and co-worker’s work showed that using a
photoiniferter-mediated polymer substrate is a simple
and direct way to make a patterned polymer surface.
This technology is very different from the commercially
used techniques of surface patterning. No photoresist
or stamp is needed for patterning, and there appears
to be more chemical flexibility with this technology than
in present photolithography and microcontact printing
techniques. For further clarification, the technique is a
photolithographic grafting process based on polymer
grafting chemistry. The polymer forms in the exposed
area, directly from the liquid monomer, and transfers
the photomask pattern. However, there are still some
limitations in the photoiniferter patterning method
currently presented in the literature. For example, the
technique is not convenient for patterning non-water-
soluble monomers. In addition, the commercial photo-
lithographic or microcontact printing technology pro-
duces patterns on the surface of substrates, namely,
surface patterning. Neither of these approaches has yet
to report patterning of polymer substrate throughout
its thickness (i.e., throughout the bulk of the material).
Three-dimensional modification, or internal patterning,
enables one to fabricate a polymer substrate with varied
properties as a function of space.
A general methodology for making diethyldithiocar-
bamated polymer substrates is needed such that ma-
terials can be modified chemically in two or three
dimensions, with a high degree of spatial control, to
incorporate desirable properties for a diverse array of
biomaterials applications. For example, thick polymer
patterns have the potential to produce microchannels,
which would be beneficial in microfluidic applications.
Beyond surface modifications, micropatterned internal
grafts in a polymer substrate would enable regional
variations in the polymer properties in three dimen-
sions. To test the feasibility of these concepts, a meth-
acrylated carbamate molecule was synthesized as a
functional photoiniferter molecule in the present work.
This functionalized photoiniferter was then incorporated
into various polymer substrates and the ability to
generate 2-D and 3-D patterned substrates investigated.
To address these issues, photoiniferters have been
used to modify the properties of polymeric surfaces15,16
and developed as a method to prepare micropatterned
surfaces.17-22 Photoiniferters are classified as dithio-
carbamate derivatives, which means, as first proposed
by Otsu et al., that they act as an initiator, transfer
agent, and terminator.23,24 The UV photolysis of a
dithiocarbamate molecule yields a reactive carbon radi-
cal and a less reactive or nonreactive dithiocarbamyl
radical. The carbon radical is usually a benzyl radical,
which can react with a vinyl monomer to initiate a
radical polymerization. The dithiocarbamyl radical re-
acts weakly or not at all with a vinyl monomer but can
terminate the polymerization by recombining with a
growing polymer chain. When the photoiniferter is
chemically bound to a surface, a polymer chain can be
generated from the surface. Furthermore, when a pho-
tomask is used to restrict UV light incident on the
substrate surface, a pattern of grafted polymer chains
can be created.
By using a custom-designed apparatus operated by
an X-Y step motor, Matsuda and co-workers prepared
a surface upon which three to five different water-
soluble polymer regions were photografted with micro-
order precision on the same substrate.17,22 Seeding and
culture of endothelial cells on the micropatterned sur-
face yielded markedly reduced adhesion on poly(N,N-
dimethylacrylamide) and poly(2-hydroxylethyl meth-
acrylate). Poly(N-[3-(dimethylamino)propyl]acrylate po-
tassium salt) and poly(methacrylic acid sodium salt)
regions promoted cell adhesion and growth, whereas
enhanced adhesion was initially observed but then
became markedly reduced over time on poly(3-sulfopro-
pyl methacrylate potassium salt).
Exp er im en ta l Section
Ma ter ia ls. All monomers were dehibited using De-hibit 100
ion exchange resin before reaction. The following methacrylate
monomers were used in making the polymer substrate: n-
butyl methacrylate (BMA, Aldrich, Milwaukee, WI), n-hexyl
methacrylate (HMA, Aldrich, Milwaukee, WI), 2,2,3,3-pen-
tafluoropropyl methacrylate (PFMA, Aldrich, Milwaukee, WI),
and 1,2-dodecyl dimethacrylate (DDMA, Aldrich, Milwaukee,
WI). A UV photoiniferter, p-xylene bis(N,N-diethyldithiocar-
bamate) (XDT, 3M Corp., Minneapolis, MN),23,24 was used as
a co-initiator in photocured formulations (Table 1, F-I-F-II)
of substrate preparation. The addition of XDT may reduce
direct initiation from HEMA-E-In. Benzoyl peroxide (BPO,
Aldrich, Milwaukee, WI) and N,N-dimethylaniline (DMA,
Aldrich, Milwaukee, WI) were used as a bimolecular initiating
system in thermally cured formulations (Table 1, F-II-F-IV)
In Mastuda’s studies, two methods were used to make
the photoactive polymer substrates. In the first method,
a photoactive monomer, typically a vinylbenzyl N,N-
diethyldithiocarbamate, was copolymerized with sty-
rene.19 The photoactive polymer was then dissolved in
toluene solution (2 wt %) and cast on one side of a PET
film. A cross-linked polystyrene film was achieved by
irradiation with a 60Co γ-ray source. The substrate was
then used in photopatterning with monomer/water

Macromolecules, Vol. 36, No. 18, 2003
A Methacrylated Photoiniferter 6741
Ta ble 1. Su bstr a te F or m u la tion a n d P olym er iza tion Con d ition s
F-I F-II F-III F-IV
monomers (% molar ratio)
F-V
BMA
67.0
29.0
HMA
DDMA
PFMA
HEMA-E-In
32.1
35.5
2.7
32.0
35.0
3.0
88.9
30.0
1.0
2.0
1.0
1.5
8.6
29.7
30.0
13.0
58.0
0.7
CN965
XDTa
1.4
0.5
BPOa
0.5
0.5
0.45
0.45
MDAa
polymerization conditions
photocure, 1 h
photocure, 1 h
50 °C/10 h
50 °C/10 h
photocure, 1 h
a
Weight fraction by total monomer weight.
of substrate preparation. A polyester urethane diacrylate
(CN965, supplied by Sartomer Co., molecular weight ) 3000)
was also used to prepare a polymer substrate (Table 1, F-V)
for internal grafting. The following monomers were used to
make micropatterned polymer layers on the surfaces of
polymer substrates: 2-hydroxyethyl methacrylate (HEMA,
Sigma, St. Louis, MO), poly(ethylene glycol) (400) monomethyl
ether monomethacrylate (mPEG400 MA, Polysciences, War-
rington, PA), and triethylene glycol dimethacrylate (TEGMA,
Aldrich, Milwaukee, WI). HEMA was also used in internal
patterning.
Syn th esis of (Meth a cr yloyl eth ylen e-d ioxyca r bon yl)
Ben zyl N,N-Dieth yld ith ioca r ba m a te (HEMA-E-In ): th e
F u n ction a lized Mon om er In ifer ter . Briefly, 4-(chlorom-
ethyl)benzoyl chloride (2.6 × 10-2 mol, 5 g), HEMA (3.9 × 10-2
mol, 5.1 g), triethylamine catalyst (3 g), and 50 mL of ethyl
acetate (all from Aldrich, Milwaukee, WI) were added to a 250
mL round-bottom flask with a magnetic stir bar. The flask was
purged with dry N2 gas, sealed, placed in a salt-ice bath (<0
°C), and allowed to react overnight. The resulting white
powder precipitate was filtered and washed with deionized
water. Then, sodium diethyldithiocarbamate trihydrate (3.9
× 10-2 mol, 9 g) was added, and the reaction was carried out
for 5 h with continuous stirring at 60 °C. FTIR and 1H NMR
were used to confirm the structure of the product. Further
details of the synthesis are available elsewhere.25
P r ep a r a tion of N,N-Dieth yld ith ioca r ba m a ted P oly-
m er Su bstr a tes. The substrates used for patterning are based
on formulations (shown in Table 1) with varying monomer
composition and functionalized monomer-iniferter content.
Monomer solutions were cast into a glass mold and polymer-
ized either thermally at 50 °C for 10 h or photochemically for
1 h with 365 nm UV light at ∼10 mW/cm2 (BlakRay),
depending on the formulations. Because the substrate contains
the monomer-iniferter, the substrate can be used to pattern
polymer layers on the surface under simple masking and
irradiation conditions. In addition, all of the substrates contain
a high concentration of dimethacrylate cross-linker. Highly
cross-linked architectures prevent the substrates from swelling
when placed in contact with various monomer solutions during
grafting.
P r ep a r a tion of Micr op a tter n ed P olym er s. Schematic
diagrams of the devices and procedures used for micropat-
terning are shown in Figure 1. For surface patterning,
substrate formulations of F-I to F-III were used. Upon polym-
erization, a piece of polymer substrate was placed on a support
glass slide, and glass spacers with thicknesses of 100-200 µm
were used to control the spacing between the photomask and
the substrate as well as spread the grafting monomer uni-
formly over the substrate. A commercially available light
source (Novacure, EFOS) equipped with a liquid light guide
and a 365 nm band-pass filter were used to initiate surface
and internal grafting polymerization. A photomask with a slit
width of 180 µm and interslit distance of 42 µm was used to
create the surface patterns. The monomer layer and polymer
substrate were irradiated for 1-40 min by UV light transmit-
ted through a collimating lens and the photomask. A light
intensity of 70 mW/cm2 (with the 365 nm filter) was measured
at the substrate surface. During photopolymerization, the
temperature of the polymerized samples was maintained at
F igu r e 1. Schematic diagram of the microlithography surface
modification principle and method.
ambient conditions. Afterward, the irradiated sample was
thoroughly rinsed with distilled water and acetone to remove
unreacted monomer and homopolymers and subsequently
dried in air.
For internal patterning, substrate formulation F-IV was
used. To create the internal grafts, the substrate was swollen
in a HEMA solution that contained 0.2 wt % of a methacry-
lated dye (Red-MA, the dye was used so that we could easily
visualize internal micropatterned grafts) for at least 2 days
(until the substrate was uniformly red in color). The swollen
substrate was then contacted with a photomask directly and
exposed to patterned UV light for 10-15 min (Figure 1). The
exposed substrate was then swollen in chloroform and ethyl
acetate for 48 h at ambient condition to extract unreacted
monomer and soluble, unattached polymer chains. The wash-
ing step was processed until no significant double bond peak
(6165 cm-1) was observed in near-IR spectra. This methodology
has been described previously.25,27 The remaining, incorporated
Red-MA-HEMA copolymer grafts were readily visualized using
light microscopy by distinct, spatially varying color patterns
compared to the unmodified, colorless substrate regions. To
synthesize the Red-MA, Dispersed Red 1 (Aldrich, Milwaukee,
WI) was methacrylated by reacting the dye with methacrylol
chloride in chloroform/triethylamine solution. After purifica-
tion, 1H NMR was used to verify the methacrylated structure.
P r ep a r a tion of Su r fa ce-An ch or ed , Micr op a tter n ed
Hyd r ogels. The hydrogel was synthesized from a monomer
formulation of 5 wt % sodium methacrylic acid (Aldrich,
Milwaukee, WI), 80 wt % methoxylpoly(ethylene glycol) 200
methacrylate (PEG200MA) (Aldrich, Milwaukee, WI), and 15
wt % deionized water. Chain transfer leads to the formation
of a cross-linked network. A highly cross-linked polymer
substrate was placed on a support glass slide. The monomer
to be grafted was placed on the substrate along with glass
spacers (300 µm thick) to control the spacing between the
photomask and the substrate as well as spread the monomer

6742 Luo et al.
Macromolecules, Vol. 36, No. 18, 2003
uniformly over the substrate (F-I in Table 1). A commercially
available light source (Novacure, EFOS), equipped with a
liquid guide and a 365 nm filter passed through a collimating
lens, was used to initiate grafting. To create the surface-
patterned gel, a photomask of square grids (62 µm bars
separated by 438 µm) was used. The top monomer solution
and polymer substrate were irradiated for 10 min with 70 mW/
cm2 of UV light as measured at the substrate surface. After
irradiation, the sample was thoroughly rinsed with distilled
water and acetone to remove unreacted monomer and soluble
polymer and then dried in air.
confirm the presence of reactive dithiocarbamate groups.
The dithiocarbamate unit and benzene ring are unique
to the monomer-iniferter molecule in the substrate
formulations. Characteristic peaks from both of these
groups are observed in the ATR-FITR spectra of the
polymer substrates (Figure 2). Figure 2 also shows that
almost complete conversion of the double bonds is
obtained in both the photochemically or thermally cured
substrates. In addition, quantitative ATR-FTIR results
reveal that the higher the concentration of monomer-
iniferter used in the substrate formulation (e.g., F-I vs
F-II), the higher the concentration of dithiocarbamate
groups (1485, 1267 cm-1) in the substrate. This higher
concentration correlates to a higher concentration of
initiator sites for surface-mediated polymerization.
Su r fa ce P a tter n in g. Figure 3 demonstrates that
micropatterns are readily transferred from a photomask
to polymer substrates with a variety of preparation
methods and iniferter concentrations. Figure 3a shows
the geometric features of the photomask used in surface
patterning. If the patterned stripes of grafted polymer
(stained areas in Figure 3b-d) are compared to those
of the photomask, it is readily observed that their
dimensions are preserved with high fidelity. Figure 3b,c
demonstrates that, independent of the substrate prepa-
ration method, micropatterns can be transferred by UV
irradiation and surface grafting. Also, because the F-II
substrate contains less photoiniferter groups, it took a
longer exposure time to achieve realistic patterning.25,27
In str u m en ts a n d Su r fa ce Ch a r a cter iza tion . Infrared
spectra and near-infrared spectra were recorded with a Nicolet
1
Magna-IR 750 II spectrometer at 4 cm-1 resolution. H NMR
spectra of the functionalized monomer-iniferter were collected
on a Varian VXR300S Unity spectrometer. Samples were
dissolved in CDCl3 containing 1% TMS as an internal refer-
ence.
The chemical structure of the outermost substrate surface
layer was characterized by FT infrared spectroscopy (a Nicolet
Magna-IR 750 II) at 4 cm-1 resolutions. The surface topogra-
phy of each micropatterned substrate and its thickness were
characterized using light microscopy with a Nikon Optic
system (S & M Microscopes, Inc.). The spatial dimensions of
the grafted layers were standardized by known dimensions of
the photomask. Dyes were used to enhance the contrast
between chemically modified regions. The grafted hydrophilic
polymer regions were stained with an aqueous basic blue
(Aldrich, Milwaukee, WI) solution, which stains the hydro-
philic polymer regions blue, independent of pH. In addition,
an aqueous Rose Bengal (Aldrich, Milwaukee, WI) solution was
also used to stain the hydrophilic polymer regions, which
stains the polymer red at pH < 7. Controls demonstrated that
the dye did not stain the hydrophobic polymer substrates used
in these studies (results not shown).
Resu lts a n d Discu ssion
Su bstr a te Ch a r a cter iza tion . As presented in Fig-
ure 1, the micropatterning technique proposed here
utilizes UV light to initiate polymerization at specific
regions of the polymer substrate. The radicals formed
in these regions initiate polymerization of the mono-
mer’s vinyl groups in solution to covalently graft thin
layers of polymer to the substrate. After removing
unpolymerized monomer and soluble homopolymer, the
surface-anchored polymer layer or internal grafted
polymer remains as the new micropatterned region.
The purpose of the newly synthesized monomer-
iniferter (HEMA-E-In) is to introduce photoiniferter
groups along the internal chains of a cross-linked
polymer substrate, so that the dithiocarbamate group
can be employed to initiate further photografting. The
methacrylic double bond in HEMA-E-In allows copo-
lymerization with other components in the substrate
formulation (Table 1), so that the dithiocarbamate group
is covalently incorporated throughout the polymer,
including the surface of the polymer substrate. Polymer
substrates can be prepared without using additional
initiators, like XDT or BPO. It was demonstrated in
previous work that surface grafting could be achieved
using substrates prepared solely by photoinitiation of
HEMA-E-In.25,27 The purpose of using XDT or thermal
initiators to polymerize the initial polymer substrate is
to maintain the unreacted form of the dithiocarbamate
group on the poly(HEMA-E-In). This may not be im-
portant for surface patterning; however, it is very
important for internal patterning because grafting is
conducted from internal chains of a cross-linked polymer
substrate.
To enhance our understanding of the unique effects
of the photoiniferter chemistry, a photoinitiator (not a
photoiniferter), DMPA, replaced the photoiniferter in
certain substrate formulations. In these substrates
(polymerized without the iniferter) no patterning or
grafting was observed. These results illustrate that the
photoiniferter chemistry is capable of making covalently
bound polymer layers.
In ter n a l P a tter n in g. As indicated by the ATR-
FTIR spectra and surface patterning results, the dithio-
carbamate group of the monomer-iniferter is chemically
bound to the surface of the polymeric substrate during
copolymerization. Actually, the dithiocarbamate group
is not only attached to the surface of the substrate but
is also present throughout its entire structure since the
methacrylate group in the HEMA-E-In molecule is
polymerized homogeneously throughout the cross-linked
polymeric network of the substrate. To support this
claim, a loosely cross-linked substrate network (F-V)
was cured and swollen in a HEMA solution with 0.2 wt
% Red-MA as a polymerizable dye. After the system
reached equilibrium in its swollen state, a patterning
experiment was performed with an irradiation time of
∼10-15 min. After removing the unreacted monomer
and homopolymers, the internal patterning appears,
indicating covalently grafted dye throughout the poly-
mer network.
Figure 4 presents the results for internal patterning.
The side view (Figure 4b) clearly shows that the grafts
grow throughout the substrate; however, the dye par-
tially absorbs the UV light. Since the substrate is about
2 mm thick, the grafting did not occur throughout the
ATR-FTIR spectroscopy was used to verify the
chemical composition of the polymer surfaces and to

Macromolecules, Vol. 36, No. 18, 2003
A Methacrylated Photoiniferter 6743
F igu r e 2. Comparison of the ATR-FTIR spectra of the
substrates containing various photoiniferter concentrations.
Curve 1: F-IV, thermally polymerized; curve 2: F-I, photo-
cured; curve 3: F-II, photocured.
F igu r e 4. Internal grafting and patterning with various
resolution. Substrate formulation is F-V. (a) Top view of an
internal pattern, mask width 1 mm, 15 min irradiation. (b)
Side view, same sample as (a). (c) Top view of an internal
pattern, mask width 20 µm. (d) Same sample with (c) at lower
magnification.
F igu r e 3. Comparison of surface micropatterning with vary-
ing concentrations of photoiniferter in the substrates. HEMA
was grafted onto the substrate surface. (a) Mask, (b) F-I, 10
min irradiation; (c) F-II, 40 min irradiation; (d) F-III, 3 min
irradiation.
entirety of the substrate with the limited exposure time.
Parts a and b of Figure 4 are patterns developed with a
mask of 5000 µm bars. To achieve higher resolution, a
mask with a 20 µm bar width and 20 µm pitch width
was used. Figure 4c,d shows that high-resolution pat-
terning was achieved successfully, but there is also some
graft spreading. Factors affecting the fidelity of this 3-D
process include the thickness of the substrate, exposure
time, and collimation of the light source. The precision
of 3-D pattern transfer is a focus of current, ongoing
work.
This observation suggested that the hydrophilic HEMA
monomer grafted not only on the surface of the substrate
but also internally when the monomer is allowed to
penetrate the reactive substrate. It is believed that novel
materials can be produced by the internal-grafting
method, and these materials would exhibit unique
properties such as regional swelling and absorption.
F igu r e 5. Capability for thickness control for the surface
patterned polymer. (a) Thickness as a function of irradiation
time, PEG400 MA as graft monomer F-II substrate formula-
tion. (b) Side view of a thick patterned polymer layer, TEGMA
as patterned monomer, F-II substrate formulation.
mance of an implant. With such enhancements in mind,
Figure 5 illustrates that the present technology has the
capability to control the thickness of the patterned
polymer layer. Figure 5a shows that the average thick-
ness of a patterned polymer layer, grafted by poly-
(ethylene glycol) MA, increases almost linearly with
irradiation time. After 4 min of UV irradiation, the
thickness was approximately 52 ( µm. Such a thickness
correlates to a molecular weight of graft polymer around
∼5.0 × 107 if the polymer remains linear and is not
Th ick n ess Con tr ol of th e Micr op a tter n ed P oly-
m er La yer . In biomedical applications, topographic
modulation of tissue response is believed to be one of
the most important considerations in the design and
manufacture of a biomaterial.5 Various studies have
indicated that it may be possible to design the surface
texture of implanted materials to improve the perfor-

6744 Luo et al.
Macromolecules, Vol. 36, No. 18, 2003
with a uniform thickness of ∼300 µm and a ∼500 µm
spacing between the micropatterned parts, creating
microchannels on the substrate surface. By introducing
aqueous fluids of various pH on the device, the pH
response of the hydrogel was investigated by observing
dimensional changes in the micropatterned gel. Specif-
ically, the ability to open and close the patterned
microchannels was demonstrated as a function of time
and pH to illustrate the potential for these approaches
in fabricating microfluidic devices with controllable flow
loops. Since the gel is covalently bound to the substrate,
the device is robust and the behavior easily reversed
for multiple uses. Figure 6 shows that the microchan-
nels were completely closed in approximately 8 min once
submerged in pH ) 10 buffer solution. In the reverse
process, the microchannels opened within 5-8 min in
a pH ) 2 buffer solution.
Con clu sion s
A method to surface and internally modify polymer
substrates was developed by copolymerizing a meth-
acrylated photoiniferter with various methacrylated
monomers. This contribution illustrates the ability of
surface-anchored photoiniferter molecules to initiate a
grafting polymerization on a wide variety of polymer
substrates. The pattern transfer time is controlled by
the concentration of photoiniferter in the substrate, and
the grafted polymer layer thickness is controlled by the
exposure time. Grafted polymer layers, ranging in
thickness from a few microns to over a hundred microns,
are demonstrated. Surface patterns with dimensions on
the order of 20-40 µm are easily achieved with inex-
pensive and fairly versatile processing techniques.
Furthermore, results show that micropatterning can be
accomplished wherever photoiniferter is present, whether
on the substrate surface or within the substrate net-
work. Internal micropatterning is a unique aspect of this
method, and hydrophilic internal grafts were patterned
into a hydrophobic substrate. This simple, one-step
procedure allows 3D modifications to polymer substrates
to construct regionally modified polymer with different
degrees of hydrophobicity or other properties, such as
electric charge.
F igu r e 6. Microchannel formation on micropatterned, surface
anchored hydrogels (∼300 µm thick). Substrate formulation
is F-I. (a) Swollen in deionized water for 2 h. (b) Swollen in
pH ) 2 solution and then dried. (c) Swollen in pH 2.0 buffer
solution and then immerged into pH 10.0 buffer solution at
(d) 4 min, 5 s; (e) 5 min, 57 s; and (f) 8 min, 9 s.
cross-linked. However, chain transfer is readily occur-
ring during the surface-initiated polymerizations of
these monomers.26,27 Cross-linking occurs due to chain
transfer reactions involving the poly(ethylene glycol)
units in the monomer and leads to gelation effects and
deviations from a purely surface grafting approach.
While this leads to a higher polydispersity and deviation
from a pure grafting mechanism, this behavior can also
provide certain advantages as well, in terms of a simple
approach to modify the substrate surface properties.
The capability to construct well-defined yet relatively
thick patterned polymer layers may result in a progres-
sion from surface patterning to microfabrication for
microfluidic applications.28 As shown in Figure 5b, a
three-dimensional structure is obtained when TEGD-
MA, a divinyl monomer, is irradiated for 10 min in
contact with a HEMA-E-In substrate. The thickness of
the patterned polymer layer on top of the substrate in
Figure 5b is approximately 140 ( 20 µm. One very
important result in the experiment is that a well-defined
pattern is still maintained with this relatively thick
patterned layer. This result, along with the ability to
accurately tune layer thickness by controlling irradia-
tion time, makes this technology very attractive for a
number of applications. One important and extremely
useful application of this technique would be for con-
structing a variety of microfluidic devices for genomic
applications, RNA and DNA analysis, and high-through-
put pharmaceutical drug screening.
Ack n ow led gm en t. The authors thank the National
Institutes of Health (DE12998) and the NSF IUCRC for
Fundamentals and Applications of Photopolymerization
for their financial support of this research.
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