Here I propose to study the terminal group effects on the mean time between translocation events. This inter-event time is determined by the capture probability and, in general, should be dependent on the strength of the applied field, the polymer concentration, and the temperature. However, the capture probability should also be sensitive to the differences in the oligonucleotide terminal groups. For example, positively charged end group should have a different probability of capture than a negatively charged one. Using both chemical and enzymatic modifications, oligonucleotides bearing different number and sign of charges will be prepared. The series of oligonucleotides with differently charged terminal groups - bearing- 7e, -6e, -4e, -3e, and +4e - will be used to determine how the inter-event times, or the capture times, depend on the number of charges in the terminal groups. This process will also be compared to a simple modified charged sphere model of ion conductivity that will be developed. Combination of the terminal group series experiments and the model will provide the means to increase the number of events (decrease capture times), leading to increased fidelity and diagnostic power. Understanding this capture time will aid in the development of a high throughput sequencing device, one that will be useful in both health research and pharmacogenetics.

Agency
National Institute of Health (NIH)
Institute
National Human Genome Research Institute (NHGRI)
Type
Postdoctoral Individual National Research Service Award (F32)
Project #
5F32HG002636-02
Application #
6649702
Study Section
Genome Study Section (GNM)
Program Officer
Graham, Bettie
Project Start
2002-09-01
Project End
2004-08-31
Budget Start
2003-09-01
Budget End
2004-08-31
Support Year
2
Fiscal Year
2003
Total Cost
$46,420
Indirect Cost
Name
Harvard University
Department
Microbiology/Immun/Virology
Type
Schools of Arts and Sciences
DUNS #
082359691
City
Cambridge
State
MA
Country
United States
Zip Code
02138
Park, Stella Y; Russo, Christopher J; Branton, Daniel et al. (2006) Eddies in a bottleneck: an arbitrary Debye length theory for capillary electroosmosis. J Colloid Interface Sci 297:832-9