Anal. Chem. 2007, 79, 1064-1066
Immobilized Hydrogels for Screening of
Molecular Interactions
Melissa M. Dominguez, Michel Wathier, Mark W. Grinstaff,* and Scott E. Schaus*
Departments of Biomedical Engineering and Chemistry, Metcalf Center for Science and Engineering, Boston University,
590 Commonwealth Avenue, Boston, Massachusetts 02215
can affect molecular and macromolecular properties as well as
create unwanted molecular interactions at the surface, influencing
assay outcome and results. Eliminating the necessity for covalent
attachment or chemical modification prior to screening may
provide a means to explore a greater diversity of interactions. Such
strategies have been explored using conventional polyacrylamide
chemistry, fluorous-tagged carbohydrate substrates, and self-
assembled fibers.32-34 Herein, we report the preparation and
evaluation of immobilized hydrogels as general screening cham-
bers for molecular interactions. Specifically, we are printing
molecules and macromolecules without prior chemical modifica-
tion within three-dimensional hydrogels formed in situ using a
one-step process. Using this screening platform, we demonstrate
small molecule-protein, protein-protein, and nucleic acid-
nucleic acid molecular recognition.
Spatially arrayed, high-density microarrays enable the
rapid assessment of biological recognition events, and this
information is of widespread interest for those working
in basic research laboratories as well as in the clinic.
Today, one can find DNA, protein, or small molecule
arrays. Limitations with these systems include covalent
modification of the target complement to the array sub-
strate, array- and target-dependent setup conditions,
multiple steps, and loss of hydration at the surface. To
overcome these limitations, we have designed, prepared,
and evaluated immobilized hydrogels as general screening
chambers for small molecule-protein, protein-protein,
and nucleic acid-nucleic acid interactions. This bioma-
terial-based approach is facile, rapid, requires only one
setup protocol, and physically entraps the target comple-
ment within the polymer network and thus offers advan-
tages over the conventional chips.
For efficient formation of individual hydrogel chambers on a
aldehyde-modified glass surface, we evaluated two-component
Recent advances in our ability to access and analyze genomic
and proteomic information has resulted in a significant increase
in the rate at which scientific and medical advances are made.
These advances range from improved understanding of funda-
mental biological processes to the evaluation of new drug leads.
Rapid assessment of biological information is essential and relies
heavily on high-throughput screening of molecular-molecular or
molecular-cellular interactions.1-10 One area of screening that has
greatly enhanced our understanding of molecular and cellular
processes is microarray technology, which acquires biological
information in a spatially arrayed, high-density format. Many of
the current formats focus primarily on covalent attachment
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* Corresponding authors. E-mail: mgrin@bu.edu or seschaus@bu.edu.
Tel: 617-358-3429. Fax: (+) 1.617.358.3186.
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1064 Analytical Chemistry, Vol. 79, No. 3, February 1, 2007
10.1021/ac061709c CCC: $37.00 © 2007 American Chemical Society
Published on Web 01/03/2007