This research is aimed at the use of the DNA backbone to construct molecularly defined hydrocarbon fragments of graphene and graphite to form highly fluorescent assemblies. These DNA-carbon assemblies possess many of the useful photophysical characteristics of semiconductor quantum dots. However, they offer solutions to many of the limitations of those quantum dots: they are structurally homogeneous, are easily synthesized and readily conjugated to biomolecules, are cell permeable, and have little or no toxicity. This work is novel in several ways: it offers a new way to assemble layered hydrocabon (graphene) sheets with complete structural control;it offers novel bioconjugates of these unusual quantum luminescent assemblies;and it provides new labels that enable the imaging of multiple cellular antigens simultaneously. Our preliminary work has shown that such DNA-carbon assemblies (CAs) are multispectral labels that are cell-permeable and can be easily conjugated to antibodies and other proteins of interest. To develop these DNA-CAs for biomedical applications, however, more work is needed. Our specific research plans are to vary CA size and geometry systematically to gain an improved understanding of how structure influences their basic photophysical properties. Using this knowledge, we will construct CAs emitting in a wide range of wavelengths for practical applications in multispectral imaging;we will develop new strategies for their bioconjugation;and we will then apply them in imaging biologically and clinically relevant antigens by two approaches. This research will be important both to basic biomedical science and to applied biomedicine. Our approach offers complete structural control over nanometer-scale layered carbon assemblies, solving a major problem in the field by yielding repeatable and easily produced structures. Our structural design retains the useful photophysical properties of quantum dots, while addressing many of their major limitations in biological applications: difficult conjugation, polyvalency, poor solubility, toxiciy, poor cell permeability. We expect near-term useful results from this work, including labels that can be broadly applied in biological imaging, and demonstration of improved methods for multiantigen imaging in diagnosis of B-cell lymphomas.

Public Health Relevance

Nanometer-scale fluorescent quantum dots have highly useful properties for imaging species in biological systems;however, they are large, they can be difficult to attach to biomolecules and difficult to deliver into cells, and are often toxic. We wil address these problems by developing a new class of nanometer-sized fluorescent carbon assemblies, building them layer-by-layer using DNA as a scaffold. This work will provide valuable tools for imaging biological molecules in biomedical research, and for diagnosis of disease in the clinic.

Agency
National Institute of Health (NIH)
Type
Research Project (R01)
Project #
1R01GM106067-01A1
Application #
8625180
Study Section
Enabling Bioanalytical and Imaging Technologies Study Section (EBIT)
Program Officer
Lewis, Catherine D
Project Start
Project End
Budget Start
Budget End
Support Year
1
Fiscal Year
2014
Total Cost
Indirect Cost
Name
Stanford University
Department
Chemistry
Type
Schools of Arts and Sciences
DUNS #
City
Stanford
State
CA
Country
United States
Zip Code
94304