Combinatorial and High-Throughput Screening of Materials ...

ACS Combinatorial Science
REVIEW
Figure 9. Cumulative mass fraction of released BSA from polymer film libraries polymer release kinetics demonstrated chemistry dependent trends of
decreasing protein release with increasing polymer hydrophobicity (CPH content). The informatics based models show a robust level of agreement with
experiments (CPH, carboxyphenoxy hexane; SA, sebacic anhydride). 104
of dendritic cells (DCs). Petersen et al. 105 have built combinatorial
libraries that utilized the known measures of DC activation as a
means to more rationally design biodegradable adjuvants for
vaccine development. Adjuvant properties, such as enhancing
immunogenicity have been investigated by developing a multiplexed
polyanhydride library, that also explored the role of polymer
films and nanospheres using a novel method for high-throughput
nanosphere fabrication.
The concomitant use of this multiplexed technique and the
informatics analysis have permitted rapid optimization of the
CPH:SA polyanhydride system for use in tissue engineering
(where biocompatibility is desirable) or vaccine delivery (where
enhanced innate immune responses are desirable). The developed
multiplexed method was able to clearly demonstrate that
the chemistry of the polymer played a major role in up-regulating
cell surface marker expression and cytokine production when
films or nanospheres were used to stimulate DCs. The informatics
analysis employed in this study defined the clear differences
between these two effects (chemistry and device geometry) and
showed that the CPH:SA system has immunomodulatory capabilities
to regulate both cellular expression of surface markers and
production of cytokines. This rapid and multiplexed investigation
of the adjuvant effect (five different polymer film chemistries and
six different nanosphere chemistries with multiple replicates) was
made possible by the use of a novel multiplexed approach to
fabricate nanospheres and films and screen their interactions with
immune cells. This generality of the technique paved the path for
rational design and development of biomaterials for specific
applications in drug/vaccine delivery and tissue engineering. The
use of data dimensionality reduction methods on combinatorially
derived data provides a very powerful means to uncover structureprocessing-property
relationships that otherwise may be difficult to
detect. Figure 10 shows an example of a clear discrimination in the
behavior of polymers in for the form of nanoparticles versus flat
films in terms of their efficacy for drug delivery. This example
serves to highlight the value of informatics in linking information
across length scales.
3. MATERIALS DEVELOPMENT EXAMPLES
The CHT experimentation technologies have the broad
applicability in discovery and optimization of new materials.
Figure 10. PCA biplot comparing the polyanhydride nanosphere and
film systems showing inverse correlations with clusters in opposite
quadrants. The IL-12 production is strongly associated with the nanospheres
while the IL-6 production is more associated with the film
geometry. IL-2 and IL-6 are terms associated with different types of
cytokines which are chemical messengers capable of mediating several
facets of the immune response. 105
The areas that are most impacted by the CHT approaches
include catalysis, electronic and functional materials, polymerbased
industrial coatings, sensing materials, and biomaterials.
The CHT experimentation advances in these areas are reviewed
in sections 3.1 3.5.
3.1. Catalysis. Catalyzed reactions range from fine chemicals
to bulk chemicals, to pharmaceuticals, and to refinery chemicals.
In general, about 90% of all chemical processes are catalyzed. 106
A classical compartmentation of catalysis is into heterogeneous
and homogeneous catalysis (see Figure 11). In practical industrial
applications, 80% of all catalysts are heterogeneous catalysts
and 15% are homogeneous catalysts. The remaining 5% are
biocatalysts. 107,108 The figures of merit of catalysts performance
include sensitivity, cost, separation from products, selectivity,
and catalyst design. 109 The design of a catalyst coming from
the Latin word designare, which means identifying describes
the process of finding a new catalyst for a special reaction or the
improvement of an existing reaction in order to make the whole
process more effective (for example, more economic). It is the
starting point of a series of subsequent items including synthesis
589 dx.doi.org/10.1021/co200007w |ACS Comb. Sci. 2011, 13, 579–633