Our vision is to combine nanotechnology with proven genetic screening technology to provide non-invasive, low cost, rapid screening for specific molecular signatures of cancer. Highly sensitive and specific, DOVAM-S (Detection of Virtually All Mutations-SSCP) is capable of screening several human genes for mutations with virtually 100% accuracy. The key technology to be demonstrated is a nanofabricated, electrophoretic microdevice for detecting mutations and polymorphisms of virtually all types. With this technology, cost-effective screening for cancer predisposition could be implemented in the relatively near term. Based on the unique properties of carbon nanotubes, we envision an integrated nano-DOVAM-S system with significantly reduced reagent volumes, shortened amplification and separation times, and automated readout and interpretation of results. In this proposal, we present this vision, and the necessary steps toward a proof-of-concept demonstration: first proving that SSCP is possible with carbon nanotube arrays, followed by protocol development and comparison with standard DOVAM-S in clinical mutation screening experiments. Other efforts to develop on-chip DNA analysis technology lack the essential advantages that distinguish DOVAM-S from competing approaches to mutation screening. These are a virtually 100% detection rate and the ability to multiplex samples. In order to be effective, mutation screening by DOVAM-S requires electrophoretic separation of single- stranded DNA with and without mutations. Our approach is to use carbon nariotubes as a solid-state nanometer-scale sieve for electrophoretic separation of single-strand DNA, replacing the cross-linked polymers used in conventional gel electrophoresis. Competing efforts to provide on-chip DNA analysis retain the use of cross-linked polymers, and many are based on hybridization reactions, which cannot attain the 100% detection of mutations that has been demonstrated in the DOVAM-S approach advocated here. Nano-DOVAM- S will be validated using the human factor VIII and IX genes and the ATM gene, mutated in certain cancers.

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Exploratory/Developmental Grants (R21)
Project #
1R21CA094408-01
Application #
6440122
Study Section
Special Emphasis Panel (ZCA1-SRRB-U (O1))
Program Officer
Wagner, Paul D
Project Start
2002-04-17
Project End
2004-03-31
Budget Start
2002-04-17
Budget End
2003-03-31
Support Year
1
Fiscal Year
2002
Total Cost
$162,800
Indirect Cost
Name
City of Hope/Beckman Research Institute
Department
Type
DUNS #
City
Duarte
State
CA
Country
United States
Zip Code
91010