Quantum dots have the potential to revolutionize biological imaging due to their exceptional photophysical properties. However, precise control over the interfacial chemistry between QDs and other biomolecules remains a significant synthetic challenge limiting their broad application in biology. Common strategies for preparing QD-biomolecule conjugates generate products with poorly defined valency, relatively large hydrodynamic size, and limited modularity. To address these issues and hence to establish higher-performance and more versatile QD imaging probes, we propose an innovative synthetic approach, termed "steric exclusion". The method uses a functionalized steric-exclusion oligonucleotide designed to wrap the QD as it reacts and thereby limits the extent of the reaction to a species of fixed valency. We propose to (i) perform the single-step complete conversion of QDs to bioimaging probes that are small (<12 nm), modular, highly-specific, and monovalent;and (ii) demonstrate the utility of these probes in a challenging single- molecule imaging application by elucidating the dynamics of Notch and its processing intermediates on the surface of live cells. Ultimately, we propose to transform QDs from "probes for special purposes" to "versatile and ready-to-use bioprobes," accessible to scientists from any discipline.

Public Health Relevance

The proposed optical probes with extreme brightness, high-resolution, and photostability will provide specific and sensitive diagnostic tools. Moreover, Notch signaling is an important protein involving development and many diseases such as cancer, multiple sclerosis, lymphoma, and other diseases, and thus understanding of Notch dynamics will be beneficial for diagnostic and therapeutic purposes.

Agency
National Institute of Health (NIH)
Institute
National Institute of Biomedical Imaging and Bioengineering (NIBIB)
Type
Exploratory/Developmental Grants (R21)
Project #
1R21EB018044-01A1
Application #
8702869
Study Section
Nanotechnology Study Section (NANO)
Program Officer
Liu, Christina
Project Start
2014-03-01
Project End
2016-02-29
Budget Start
2014-03-01
Budget End
2015-02-28
Support Year
1
Fiscal Year
2014
Total Cost
$224,358
Indirect Cost
$74,358
Name
University of California San Francisco
Department
Otolaryngology
Type
Schools of Medicine
DUNS #
094878337
City
San Francisco
State
CA
Country
United States
Zip Code
94143