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