Biomedical Engineering Reference
In-Depth Information
on gold surfaces [91,92]. In such a process, soft lithography was applied to create patterned surfaces
using a combination of SAMs and microcontact printing (µCP). The two key features of soft lithog-
raphy are the use of elastomeric (i.e., mechanically soft) materials to fabricate the pattern transfer
elements by molding and the development of techniques that pattern complex biochemicals [93].
Usually, PDMS was chosen as the stamp material because of its appropriate mechanical properties,
transparency, nontoxicity, and hydrophobicity. Efforts were devoted by other groups to increase the
accuracy of patterning, easy process, and high resolution in patterns [27,64,94-100]. The patterned
materials on a fl at substrate usually represent different physical and chemical properties compared
with an uncovered space. So far, different materials, including polymers, DNA, nanoparticles,
receptors, and extracellular matrix proteins have been patterned.
The combination of SAMs and µCP was able to create patterns consisting of regions that
encouraged protein adsorption or cell adhesion, alternated with regions that discouraged such an
interaction [92]. However, the process required not only the use of metal coatings, but also alkane-
thiols or silanes as the ink. In addition, only small areas of micropatterns can be generated through
stamping. So, how to create micropatterns on a larger scale is of great interest. Introduction of LbL
self-assembly in this fi eld has led to promising progress, especially in the production of large-scale
micropatterns on conventional silicon wafers [95,101]. Applying silicon-based lithographical tech-
nology has one obvious advantage in that industrial-scale process may be feasible. Three major steps
are involved in such a combined process: (1) a photoresist is patterned through a mask by the standard
UV-irradiation procedure; (2) the substrate is then entirely covered with polyelectrolyte multilayers
and nanoparticles through standard LbL self-assembly process; and (3) micropatterns are created by
lifting off polyelectrolyte/nanoparticle fi lm above the photoresist in organic solvent acetone. This
method can be compared to the micropatterning of a thiol compound on gold supports and further
LbL assembly of multilayers [94]. Both methods gave patterns of approximately the same quality,
with clear support surfaces between the pattern features, minimal feature sizes of approximately
1-2 µm, and edge roughness of approx 0.1-0.2 µm. However, the lithographic approach is compat-
ible with existing silicon micromanufacturing technology. For industrial applications, this provides
an opportunity to use conventional lithographic technology to produce 4-in. diameter silicon wafers
completely covered with LbL self-assembled polyelectrolyte/nanoparticle patterns.
In another attempt, micro/nanostructures were directly patterned on silicone rubber through the
µCP method [27]. A PDMS stamp with microchannel structures was fi rst coated with polyelectrolyte/
microparticle multilayers through LbL self-assembly. Pretreatment of PDMS stamp with oxygen
plasma or other methods can create a hydrophilic surface for polyelectrolyte layers deposition,
but may not be necessary. Next, assembled polyelectrolyte/microparticle multilayers were trans-
ferred onto an unmodifi ed silicone rubber surface by contact printing and resulted in well-defi ned
micropatterns. On SEM examination, the resolution, stability, and accuracy of micro/nanosphere
patterns correspond to the standard of the µCP technique. Polylysine/gelatin bilayers were further
deposited on established micropatterns, and selective adhesion of endothelial cells was observed.
The unpatterned area was bare silicone rubber, which had a high-hydrophobicity, representing an
unfavorable surface for cell attachment. The mechanism of pattern transfer is not clear, but the most
probable explanation is that binding between the hydrophobic surface of silanized glass and proteins
is stronger than the adhesion force between the proteins and the silicone rubber surface [102].
In LbL self-assembly-assisted micropatterning for cell adhesion, it is essential to establish a
prepattern as the fi rst step. The patterned materials should be hydrophilic and charged for further
introduction of biocompatible polyelectrolytes, which are favorable for cell adhesion. The distance
between patterned areas can be controlled from tens of micrometers to hundreds of microns depend-
ing on a specifi c application. The unpatterned areas may be modifi ed to seed different cell types,
and this was demonstrated in a recent study by the Langer group [64]. In the process, HA patterns
were fi rst created on glass substrate with the help of a PDMS mold. Then, addition of fi bronectin
led to selective deposition on the non-HA areas. Cell type A (fi broblast NIH-3T3) only adhered onto
fi bronectin-covered area and was rejected by HA-covered patterns. Further coating of positively
