Arrayed Imaging Reflectometry
Simple methods for detecting and quantifying proteins in a multiplex (many proteins at once) fashion would potentially have considerable utility in the construction of point-of-care diagnostic devices, as well as tools for basic studies in biology and medicine. One technique under study by our group is Arrayed Imaging Reflectometry, a method whereby an antireflective coating (
a in the figure) on a silicon chip is perturbed by protein binding (
b) resulting in reflected light that’s proportional to the amount of protein bound.
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Dynamic Combinatorial Chemistry
Identifying high-affinity small molecule binders for medically relevant drug targets typically involves the iterative synthesis of large numbers of compounds. What if we could set up a system whereby small molecule fragments could undergo recombination in the presence of the target of interest, thereby allowing selection and amplification of the highest affinity binder? This idea, originally developed by a few labs (including ours) in the late 1990s, has developed into a vibrant field known as
Dynamic Combinatorial Chemistry or
Dynamic Covalent Chemistry (DCC).
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Silver Nanoparticle Surfaces for DNA Detection
DNA detection systems are becoming increasingly important in medical diagnostics. We are exploring the use of surface-immobilized silver nanoparticles functionalized with fluorophore-tagged hairpin DNA probes as sensitive “self-labeled” DNAsensors. The silver nanoparticles provide quenching of the fluorophore in the absence of target DNA.
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Solving the Sequence-Selective RNA Binding Problem
Through the efforts of a number of laboratories, we now have a
code that allows us to synthesize high-affinity, high-selectivity ligands for DNA if we know the sequence. Developing an analogous code for RNA constitutes a landmark challenge in science. Using Resin-Bound Dynamic Combinatorial Chemistry (RBDCC) to expand on a general design hypothesis for RNA-binding compounds, we identified the first synthetic compounds able to bind (CUG) repeat RNAs, a
toxic RNA important in type 1 myotonic dystrophy.
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Ultrasensitive Optical Detection of Viruses with Silicon 2-D Photonic Bandgap Structures
Direct single- or near-single copy detection of viruses is an important challenge in human health. Applications include the need to monitor emerging viral threats (H5N1 influenza and the SARS virus, for example), and the importance of understanding the long-term implications of nearly undetectable reservoirs of infection following antiretroviral therapy for HIV.
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