Expanding the performance of the sequencing-by-synthesis technology, this group will develop a cost-effective method to fabricate universal DNA nanoarrays using nano-contact printing. The current photolithography technology can cause damage to DNA probes, which the group will strive to avoid by using nano-contact printing. With the nano-sized features, a DNA nanoarray can also improve throughput by offering the ability to accommodate billions of DNA molecules in a small area. Hybridization will be detected by atomic force microscopy.
Carlos H. Mastrangelo, Ph.D., Case Western Reserve University, Cleveland,$815,000 (3 years),"Large-Scale Nanopore Arrays for DNA Sequencing"
This team will aim to develop highly integrated arrays of nanopores that can be fabricated by lithographic methods, along with on-chip silicon-based electronic circuits and circuit techniques that amplify and isolate their various electrical signals. This group will also design a dipole-sensing methodology, which in principle can distinguish signals from each of the DNA bases. Arrays of nanopores will be constructed on silicon substrates using a self-aligned compositional approach. Quadrature dipole moment detectors will be constructed that yield a signal independent of the rotation of the DNA molecule relative to the electrodes.
Jens Gundlach, Ph.D., University of Washington, Seattle,$605,000 (2 years),"Engineering MspA for Nanopore Sequencing"
The passage of single-strand DNA through a nanometer-scale pore is driven by an electric field revealing information about the DNA sequence. This method has the potential to become an inexpensive, ultrafast DNA sequencing technique. Most nanopore sequencing approaches involve either the protein pore alpha-hemolysin or artificial pores in inorganic materials. This team will use protein-engineering
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Source:NIH/National Human Genome Research Institute