DNA analysis and sequencing is at the heart of all genome projects and most if not all research in molecular, cellular, and developmental biology. It is a major part of modern medical and forensic practice, and these trends in analytical and functional genomics will continue to accelerate for the foreseeable future. Thus the need for new and different ways to sequence and analyze DNA has long been recognized. Current methodologies are relatively slow, the capital costs are high, and they are not very portable. They also require skilled technical staff, usually concentrated in special units within University, Medical, and Industrial settings. Here we propose some solutions to DNA analysis and sequencing speed, cost, and portability. Devices fabricated on silicon and quartz wafers capable of handling fL to mu L volumes, and with analysis speeds of seconds rather than minutes, hours, or days, are discussed and new research with these devices is proposed. At the heart of each device is an entirely synthetic separation matrix fabricated from SiO posts of various sizes and shapes. The central idea is to continue to exploit advances in the semiconductor industry to manufacture these devices. Our approach utilizes recent advances in patterning and etching on the nano and micro scale combined with new insights into the physical basis for DNA separations.

Agency
National Institute of Health (NIH)
Institute
National Human Genome Research Institute (NHGRI)
Type
Research Project (R01)
Project #
5R01HG001506-10
Application #
7015605
Study Section
Genome Study Section (GNM)
Program Officer
Schloss, Jeffery
Project Start
1996-08-01
Project End
2008-02-29
Budget Start
2006-03-01
Budget End
2007-02-28
Support Year
10
Fiscal Year
2006
Total Cost
$687,459
Indirect Cost
Name
Princeton University
Department
Biochemistry
Type
Schools of Arts and Sciences
DUNS #
002484665
City
Princeton
State
NJ
Country
United States
Zip Code
08544
Wang, Yufang; Guo, Ling; Golding, Ido et al. (2009) Quantitative transcription factor binding kinetics at the single-molecule level. Biophys J 96:609-20
Loutherback, Kevin; Puchalla, Jason; Austin, Robert H et al. (2009) Deterministic microfluidic ratchet. Phys Rev Lett 102:045301
Tung, Chih-Kuan; Riehn, Robert; Austin, Robert H (2009) Complementary metal oxide semiconductor compatible fabrication and characterization of parylene-C covered nanofluidic channels with integrated nanoelectrodes. Biomicrofluidics 3:31101
Ungun, Baris; Prud'homme, Robert K; Budijon, Stephanie J et al. (2009) Nanofabricated upconversion nanoparticles for photodynamic therapy. Opt Express 17:80-6
Golding, Ido; Cox, Edward C (2008) Chapter 8: Spatiotemporal dynamics in bacterial cells: real-time studies with single-event resolution. Methods Cell Biol 89:223-51
Morton, Keith J; Loutherback, Kevin; Inglis, David W et al. (2008) Crossing microfluidic streamlines to lyse, label and wash cells. Lab Chip 8:1448-53
Morton, Keith J; Loutherback, Kevin; Inglis, David W et al. (2008) Hydrodynamic metamaterials: microfabricated arrays to steer, refract, and focus streams of biomaterials. Proc Natl Acad Sci U S A 105:7434-8
Austin, Robert H; Lim, Shuang-fang (2008) The Sackler Colloquium on promises and perils in nanotechnology for medicine. Proc Natl Acad Sci U S A 105:17217-21
Keymer, Juan E; Galajda, Peter; Lambert, Guillaume et al. (2008) Computation of mutual fitness by competing bacteria. Proc Natl Acad Sci U S A 105:20269-73
Galajda, Peter; Keymer, Juan; Chaikin, Paul et al. (2007) A wall of funnels concentrates swimming bacteria. J Bacteriol 189:8704-7

Showing the most recent 10 out of 38 publications