The long-term goal of this research is the development of a rapid DNA sequencing method based on scanning tunneling and atomic force microscopy and newly developed microscope tips. Our approach attempts to overcome three serious limitations of current sequencing methods-the need to sub- clone DNA in kilobase fragments, the restriction of chemical sequencing methods to roughly kilobase lengths of DNA, and the difficulties inherent in sequencing long repetitive sequences. To overcome these serious obstacles to rapid sequencing, we propose to (1) develop methods for clamping long single strands of DNA to substrates so they can be followed over 10-100 kilobases, and (2) devise novel microscope tips designed to recognize the adsorption spectra of individual purines and pyrimidines. Our proposed new methods clamp the DNA to substrates using well-understood physical and chemical principles and recent advances in tunneling microscopy. The proposed methods do not depend on atomic scale resolution, and in principle accelerate the sequencing speed by many orders of magnitude.

Agency
National Institute of Health (NIH)
Institute
National Human Genome Research Institute (NHGRI)
Type
Exploratory/Developmental Grants (R21)
Project #
5R21HG000482-02
Application #
3443861
Study Section
Genome Study Section (GNM)
Project Start
1991-09-01
Project End
1993-11-30
Budget Start
1992-09-01
Budget End
1993-11-30
Support Year
2
Fiscal Year
1992
Total Cost
Indirect Cost
Name
Princeton University
Department
Type
Schools of Arts and Sciences
DUNS #
002484665
City
Princeton
State
NJ
Country
United States
Zip Code
08544
Zimmermann, R M; Cox, E C (1994) DNA stretching on functionalized gold surfaces. Nucleic Acids Res 22:492-7