The development of new probes, homogeneous assays, and miniaturized devices that allow for the direction detection of compounds or specific binding events is having an impact in basic research, clinical diagnostics, and drug development. Novel fluorescent and luminescent technologies are especially important for the implementation of greater speed and automation. These advances are being applied to the detection, localization of gene sequences, proteins, infectious organisms, and a variety of other targets. The primary goal of this proposal is to develop a new class of biological detection labels by conjugating biological molecules to semiconductor quantum dots (nanocrystals). The quantum dots are detected by their intense photoluminescence, and the attached biomolecules recognize specific analytes such as proteins, DNA, or viruses. Recent research in our group has developed a simple procedure that allows highly luminescent quantum dots (ZnS-capped CdSe) to be solubilized in water; the water-soluble quantum dots are biocompatible and can bo covalently linked to large biomolecules (SCIENCE 281, 2106-2018, 1998). In comparison with organic dyes, this new class of luminesc3nt labels offers significant advantages such as size-tunable emission wavelength, symmetric spectral shapes, and simultaneous excitation at a single wavelength. The primary goal os this proposal is to develop a new class of biological detection by conjugating biological molecules to semiconductor quantum dots (nanocrystals). The quantum dots are detected by their intense photoluminescence, and the attached biomolecules recognize specific analytes such as proteins, DNA, or viruses. Recent research in our group has developed a simple procedure that allows highly luminescent quantum dots (ZnS-capped CdSe) to be solubilized in water; the water- soluble quantum dots are biocompatible and can be covalently linked to large biomolecules (SCIENCE 281, 2106-2018, 1998). In comparison with organic dyes, this new class of luminescent labels offers significant advantages such as size-tunable emission wavelength,, symmetric spectral shapes, and simultaneous excitation at a single wavelength. The proposed research will systematically examine a variety of quantum dot bioconjugates for biological and biomedical applications. The basic materials will include group II-VI (Cds and CdSe) and group III-V (InP and InAs) semiconductors, with emission wavelengths tunable from the blue to the near infrared. An inorganic capping layer will be used to improve the photostability and luminescence quantum yields. The capped quantum dots will be conjugated to two broad categories of biological molecules-proteins and nucleic acids. Strategies will also be developed to manipulate the quantum dot optical properties, such as the quenching of quantum dot luminescence with organic chromophores. Quantum dot bioconjugates are expected to be available in large quantities and in lyphophilized forms, for broad distribution to the scientific community.

Agency
National Institute of Health (NIH)
Institute
National Institute of General Medical Sciences (NIGMS)
Type
Research Project (R01)
Project #
1R01GM060562-01
Application #
6038989
Study Section
Special Emphasis Panel (ZRG1-BMT (01))
Program Officer
Lewis, Catherine D
Project Start
2000-03-01
Project End
2004-02-28
Budget Start
2000-03-01
Budget End
2001-02-28
Support Year
1
Fiscal Year
2000
Total Cost
$211,790
Indirect Cost
Name
Indiana University Bloomington
Department
Chemistry
Type
Schools of Arts and Sciences
DUNS #
006046700
City
Bloomington
State
IN
Country
United States
Zip Code
47401
Smith, Andrew M; Nie, Shuming (2012) Compact quantum dots for single-molecule imaging. J Vis Exp :
Shi, Chunmeng; Zhu, Ying; Xie, Zhihui et al. (2009) Visualizing human prostate cancer cells in mouse skeleton using bioconjugated near-infrared fluorescent quantum dots. Urology 74:446-51
Shi, Chunmeng; Zhu, Ying; Cerwinka, Wolfgang H et al. (2008) Quantum dots: emerging applications in urologic oncology. Urol Oncol 26:86-92
Agrawal, Amit; Deo, Rajesh; Wang, Geoffrey D et al. (2008) Nanometer-scale mapping and single-molecule detection with color-coded nanoparticle probes. Proc Natl Acad Sci U S A 105:3298-303
Gao, Xiaohu; Chung, Leland W K; Nie, Shuming (2007) Quantum dots for in vivo molecular and cellular imaging. Methods Mol Biol 374:135-45
Agrawal, Amit; Zhang, Chunyang; Byassee, Tyler et al. (2006) Counting single native biomolecules and intact viruses with color-coded nanoparticles. Anal Chem 78:1061-70
Smith, Andrew M; Dave, Shivang; Nie, Shuming et al. (2006) Multicolor quantum dots for molecular diagnostics of cancer. Expert Rev Mol Diagn 6:231-44
Gao, Xiaohu; Yang, Lily; Petros, John A et al. (2005) In vivo molecular and cellular imaging with quantum dots. Curr Opin Biotechnol 16:63-72
Agrawal, Amit; Tripp, Ralph A; Anderson, Larry J et al. (2005) Real-time detection of virus particles and viral protein expression with two-color nanoparticle probes. J Virol 79:8625-8
Smith, Andrew M; Nie, Shuming (2004) Chemical analysis and cellular imaging with quantum dots. Analyst 129:672-7

Showing the most recent 10 out of 19 publications