In numerous cancers, diagnosis timing and ultimate patient prognosis are intimately linked with early diagnosis being one of the greatest predictors of survival. Unfortunately, for many of those same cancers no simple test exists through which an early stage diagnosis is readily made. While a vast body of potential biomarkers, both protein and nucleic acid, exists and is identified in the scientific literature, the ability to detect these markers at the low levels present in biological fluids that can be collected non-invasively at early stages often proves difficult or impossible. To test the predictive value of these biomarkers, and to implement patient testing in a clinical setting for biomarkers that prove to have high predictive value, a pressing need exists for molecular detection technologies that have a rare and difficult combination of crucial characteristics including sensitivity, specificity, robustness, simplicity, and low cost. The proposed research attempts to develop just such a technique by coupling free radical polymerization initiators to genetic markers indicative of cancer's presence. Free radical polymerizations, initiated either by photoinitiation or chemical (i.e., redox) initiation are, by their nature, amplification events wherein each radical that is generated polymerizes through a large number of monomer units, each of which can be detected by a variety of means. Previously, we have shown that this technique is able to produce a macroscopically observable signal from as few as 1000 biological markers on a surface by polymerizing as many as 1011 monomers per initial surface bound molecule. Here, we propose to translate our previous success with free radical polymerizations into a viable test for determining the presence or absence of certain known genetic indicators of the presence of cancer. Ultimately, such a development would dramatically aid in cancer diagnosis, identification, treatment, and survival rates for many cancers linked to genetic anomalies. Our overall hypothesis is that utilization of free radical polymerization as a means for ultrahigh signal amplification will lead to vastly improved detection and outcomes for cancer patients. Specifically, we aim to (i) develop and enhance redox and photoinitiated free radical polymerization schemes for signal amplification in the detection of genetic biomarkers, (ii) detect panels of single base mutations using the signal amplification technique of radical chain polymerization, and (iii) detect panels of single base mutations using the signal amplification technique of radical chain polymerization from an in vivo source.In numerous cancers, diagnosis timing and ultimate patient prognosis are intimately linked: early diagnosis is one of the greatest predictors of survival. Unfortunately, for many of those same cancers no simple test exists through which an early stage diagnosis is readily made. The proposed research attempts to develop a highly sensitive, robust, facile test for genetic anomalies that occur in many cancers, andthe goal is to enable early detection, well in advance of other currently available techniques. ? ? ?
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