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

prevent the hybridization of probes to intended (or unintended) target
reagents, which will prevent the formation of a measurable duplex product
and lead to a false negative result. There may also be increased susceptibility
to cross-hybridization if the remaining single stranded target region is long
enough to form stable duplexes under the hybridization conditions. Similarly,
intramolecular structure in the target may prevent its binding to the intended
probe [30].
e. Sample homogeneity. Sample preparations are derived from cell populations
in which there is little homogeneity of type and stage [13, 58]. Transcript
levels are bound to change according to the cell cycle, environmental
conditions, and cellular type [13, 58]. There exist methods of cellular
isolation, such as laser dissection and FACS (fluorescently activated cell
sorting), or the use of synchronized cultures, that minimize the variation of
cell types and localized disease effects, although there will still be variation
in the localized environment conditions, cell cycle (unless synchronized),
stage of disease progression or response to toxicity effects [58]. Thus, no
matter how precisely one is able to target probe specificity to a gene, allele or
isoforms, the sensitivity of the experiment relates to the makeup of the
sample mixture as a whole.
2) Sensitivity and Scanner Limitations. Scanner limitations were mentioned above with
respect to the lower bound of detection, but are important to the upper bound as well.
The devices that capture photons saturate well below the limit of response of the
Microarray itself [59]. There have been attempts to adjust for this effect by lowering
13