The objective of this research is to develop a new generation of ultra-high-throughput screening (uHTS) systems based on surface-enhanced Raman scattering (SERS) detection.
The specific aims of the project are:
Aim 1. Develop a multi-spectral Raman system (MRS) as the optical readout for uHTS.
Aim 2 : Evaluate the uHTS-MRS using molecular sentinels for highly parallel ligand/target binding detection.
Aim 3 : Develop and integrate an automated system for detection of optical signals from SERS-based nanoprobes.
Aim 4 : Evaluate the CMOS-uHTS system for high throughput screening of small molecules or mRNA probes in a cellular model. Our system will offer a new dimension in label multiplexing for characterizing large numbers of samples in cell-based high-throughput screening for drug discovery. A novel SERS-based molecular-sentinel detection scheme will be applied for multiplex gene expression analysis. The unique features of the proposed system include: Novel instrumentation based on multi-spectral imaging detection Novel detection scheme based on combination of molecular recognition and SERS detection The SERS effect enhances the sensitivity of conventional Raman signal over 106-1015 fold SERS-MS nanoprobes are insensitive to photo-bleaching (often associated with fluorescent probes). Ultra high-throughput """"""""label multiplex"""""""" detection (i.e. capability for many Raman dye-labeled probes to be used simultaneously) (the extremely narrow Raman bands allow SERS to be used as a multiplexing technique). The system will be tested for screening of small molecules, synthetic chemical and natural product libraries that up- or down-regulate expression of various families of mRNA. Active compounds that are capable of modulating mRNA gene expression levels will be identified, followed by additional assays. The SERS-based uHTS instrumentation will provide a tool that has the potential to be faster and more efficient than currently available systems, and is capable to provide great sensitivity with higher levels of specificity, and multiplexing capabilities to screen synthetic chemical and natural product libraries such as the ones that will be registered and housed in the NIH-sponsored molecular libraries screening centers. ? ?

Agency
National Institute of Health (NIH)
Institute
National Institute of Biomedical Imaging and Bioengineering (NIBIB)
Type
Research Project (R01)
Project #
5R01EB006201-04
Application #
7318325
Study Section
Special Emphasis Panel (ZEB1-OSR-C (O1))
Program Officer
Korte, Brenda
Project Start
2006-03-02
Project End
2009-11-30
Budget Start
2007-12-01
Budget End
2008-11-30
Support Year
4
Fiscal Year
2008
Total Cost
$468,412
Indirect Cost
Name
Duke University
Department
Biomedical Engineering
Type
Schools of Engineering
DUNS #
044387793
City
Durham
State
NC
Country
United States
Zip Code
27705
Yuan, Hsiangkuo; Gomez, Jose A; Chien, Jennifer S et al. (2016) Tracking mesenchymal stromal cells using an ultra-bright TAT-functionalized plasmonic-active nanoplatform. J Biophotonics 9:406-13
Yuan, Hsiangkuo; Wilson, Christy M; Xia, Jun et al. (2014) Plasmonics-enhanced and optically modulated delivery of gold nanostars into brain tumor. Nanoscale 6:4078-82
Wang, Hsin-Neng; Dhawan, Anuj; Du, Yan et al. (2013) Molecular sentinel-on-chip for SERS-based biosensing. Phys Chem Chem Phys 15:6008-6015
Vo-Dinh, Tuan; Fales, Andrew M; Griffin, Guy D et al. (2013) Plasmonic nanoprobes: from chemical sensing to medical diagnostics and therapy. Nanoscale 5:10127-40
Yuan, Hsiangkuo; Fales, Andrew M; Khoury, Christopher G et al. (2013) Spectral Characterization and Intracellular Detection of Surface-Enhanced Raman Scattering (SERS)-Encoded Plasmonic Gold Nanostars. J Raman Spectrosc 44:234-239
Yuan, Hsiangkuo; Liu, Yang; Fales, Andrew M et al. (2013) Quantitative surface-enhanced resonant Raman scattering multiplexing of biocompatible gold nanostars for in vitro and ex vivo detection. Anal Chem 85:208-12
Ngo, Hoan Thanh; Wang, Hsin-Neng; Fales, Andrew M et al. (2013) Label-free DNA biosensor based on SERS Molecular Sentinel on Nanowave chip. Anal Chem 85:6378-83
Wang, Hsin-Neng; Fales, Andrew M; Zaas, Aimee K et al. (2013) Surface-enhanced Raman scattering molecular sentinel nanoprobes for viral infection diagnostics. Anal Chim Acta 786:153-8
Yuan, Hsiangkuo; Fales, Andrew M; Vo-Dinh, Tuan (2012) TAT peptide-functionalized gold nanostars: enhanced intracellular delivery and efficient NIR photothermal therapy using ultralow irradiance. J Am Chem Soc 134:11358-61
Khoury, Christopher G; Vo-Dinh, Tuan (2012) Plasmonic ""Nanowave"" Substrates for SERS: Fabrication and Numerical Analysis. J Phys Chem C Nanomater Interfaces 116:7534-7545

Showing the most recent 10 out of 32 publications