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Sample A: Cover Page of Thesis, Project, or Dissertation Proposal

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likelihood that no such structural regions f<strong>or</strong>m is vanishingly small. Because <strong>of</strong> the<br />

highly folded structures that result there can also be tertiary structures present,<br />

compounding the likelihood that the availability <strong>of</strong> intended sites f<strong>or</strong> probe binding<br />

will be sterically hindered, and greatly decreasing the diffusion constant <strong>of</strong> the<br />

molecule in solution (slowing the rate <strong>of</strong> duplex f<strong>or</strong>mation further) [29]. Shearing <strong>of</strong><br />

targets strands is thus recommended, with the goal <strong>of</strong> ending with target lengths that<br />

are approximately equivalent to probe lengths [5, 10, 35].<br />

3) Temperature. As noted above, the probe length and base composition affect the<br />

melting temperature (Tm) <strong>of</strong> any duplex, where the melting temperature is defined as<br />

the temperature at which 50% <strong>of</strong> the duplex structures are dissociated [22, 25, 26,<br />

36]. Experimental conditions are designed as a best fit f<strong>or</strong> the average <strong>of</strong> the<br />

hundreds <strong>of</strong> thousands <strong>of</strong> individual reactions occurring on the array. Solvent<br />

components can be altered to change the dielectric constant <strong>of</strong> the solution, altering<br />

the energetics <strong>of</strong> the product’s hydrogen bonds [34, 37].<br />

4) Equilibration Time. As noted above, the competition among highly similar targets<br />

f<strong>or</strong> the same complementary probe sequence requires that adequate hybridization<br />

time be allocated, in <strong>or</strong>der f<strong>or</strong> the reaction to achieve equilibrium. Sh<strong>or</strong>t hairpin<br />

structures are less energetically fav<strong>or</strong>able than long duplexes, but since unimolecular<br />

reactions occur in a much sh<strong>or</strong>ter period <strong>of</strong> time than bimolecular reactions,<br />

unimolecular reactions can kinetically trap probe <strong>or</strong> target in non-optimal f<strong>or</strong>ms[5,<br />

10] . The various kinetic properties <strong>of</strong> the tens <strong>of</strong> thousands <strong>of</strong> probes realistically<br />

prevent a significant prop<strong>or</strong>tion <strong>of</strong> probe-target interactions from achieving chemical<br />

7

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