Technology Development The focus of this renewal application is on the development of technologies that will enable the study of the human genome and the mechanisms underlying human disease at a substantially-reduced cost. Methods to analyze human samples must be extremely sensitive in order to: 1) detect low abundance biomolecules;and 2) be informative using small sample volumes. However, current genomic and proteomic methods vary widely in their suitability for analyzing human samples. For example, genomic methods such as microarrays and next generation sequencing have high sensitivity, but are limited in their quantitative value because ofthe biases of DNA amplification strategies that are required to generate detectable signals. In contrast, current proteomic methods such as ELISA assays simply lack sensitivity altogether, leaving the low abundance proteins that may be informative biomarkers undetected. In this second tier of the proposal. Technology Development, we are focused on developing technologies that can detect nucleic acids and proteins not only with high accuracy and sensitivity, but also with a minimum of time and expense in order to facilitate their translation to clinical medicine. Such technologies will equip biomedical researchers with better tools to investigate the human disease process, and enable the use of less invasive sources of diagnostic material, such as sweat, saliva, or breath. These technologies were in the innovation phase during the previous funding period and met desired milestones. Current development will be directed toward further strengthening the tools and demonstrating their improvement over existing technologies. We will develop a method based on modified atomic force microscopy for the label-free nanomechanical quantitation of nucleic acids, and two methods that integrate microfluidics and electrical impedance sensing for the high-throughput digital detection of proteins from minute samples. Once proof-of-principle has been established, these technologies will be primed for export and application to specific clinical problems.

Agency
National Institute of Health (NIH)
Institute
National Human Genome Research Institute (NHGRI)
Type
Research Program Projects (P01)
Project #
2P01HG000205-24
Application #
8730759
Study Section
Special Emphasis Panel (ZHG1-HGR-N (J1))
Project Start
Project End
Budget Start
2013-09-23
Budget End
2014-07-31
Support Year
24
Fiscal Year
2013
Total Cost
$2,278,742
Indirect Cost
$793,271
Name
Stanford University
Department
Type
DUNS #
009214214
City
Stanford
State
CA
Country
United States
Zip Code
94305
Li, Yong Fuga; Tsai, Kathleen J S; Harvey, Colin J B et al. (2016) Comprehensive curation and analysis of fungal biosynthetic gene clusters of published natural products. Fungal Genet Biol 89:18-28
Lefterova, Martina I; Shen, Peidong; Odegaard, Justin I et al. (2016) Next-Generation Molecular Testing of Newborn Dried Blood Spots for Cystic Fibrosis. J Mol Diagn 18:267-82
Nascimento, Raphael A S; Özel, Rıfat Emrah; Mak, Wai Han et al. (2016) Single Cell "Glucose Nanosensor" Verifies Elevated Glucose Levels in Individual Cancer Cells. Nano Lett 16:1194-200
Pelechano, Vicent; Wei, Wu; Steinmetz, Lars M (2016) Genome-wide quantification of 5'-phosphorylated mRNA degradation intermediates for analysis of ribosome dynamics. Nat Protoc 11:359-76
Gao, Wei; Emaminejad, Sam; Nyein, Hnin Yin Yin et al. (2016) Fully integrated wearable sensor arrays for multiplexed in situ perspiration analysis. Nature 529:509-14
Padovani, José I; Jeffrey, Stefanie S; Howe, Roger T (2016) Electropermanent magnet actuation for droplet ferromicrofluidics. Technology (Singap World Sci) 4:110-119
Emaminejad, Sam; Paik, Kee-Hyun; Tabard-Cossa, Vincent et al. (2016) Portable Cytometry Using Microscale Electronic Sensing. Sens Actuators B Chem 224:275-281
Mankos, Marian; Persson, Henrik H J; N'Diaye, Alpha T et al. (2016) Nucleotide-Specific Contrast for DNA Sequencing by Electron Spectroscopy. PLoS One 11:e0154707
Özel, Rıfat Emrah; Kahnemouyi, Sina; Fan, Hsinwen et al. (2016) Smartphone Operated Signal Transduction by Ion Nanogating (STING) Amplifier for Nanopore Sensors: Design and Analytical Application. ACS Sens 1:265-271
Steinmetz, Lars M; Jones, Allan (2016) Sensing a revolution. Mol Syst Biol 12:867

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