With the recent development of diagnostic biochips comes the potential of high-throughput, rapid genetic screening of targeted pathogens and disease biomarkers. A primary limitation associated with this technology involves the sequence specific identification of low copy number polynucleotides using clinically suitable detection instrumentation, often requiring target amplification with PCR-based methods or through signal amplification methods. Current amplification methods suffer from limitations associated with individual primer selection for each targeted biomarker, reliance on enzymatic reactions that convert a substrate into a chemiluminescent or fluorescently detectable moiety, or dependence on sophisticated instrumentation in order to detect and quantify the minute amounts of genetic target available from a patient sample. We have developed a novel, rapid, and specific signal amplification method that utilizes free radical photopolymerization to transduce signal from binding of complementary biomolecules into a macroscopically detectable response, thus eliminating the reliance of expensive instrumentation in the detection method. This approach involves coupling photointiators to DNA hybridization sites instead of fluorophores or other traditional reporter molecules to allow for the surface-initiated polymerization of detectable monomer exclusively at hybridization sites on a biochip surface. High propagation rates of acrylate monomer and low termination rates of propagating chains in highly crosslinked monomer formulations allow for high amplification factors to be achieved, as thick polymer films may be generated from minute amounts of DNA hybrids on the surface. Such an amplification system could be made inexpensive and robust while still providing a highly detectable response that is not achievable with other established amplification methods. In this communication, two separate amplification systems will be presented. The first involves coupling water soluble, photoclevable initiators onto streptavidin proteins in a high initiator to protein ratio. Incubation of this product onto commercialized biochips containing surface bound, biotin labeled DNA molecules followed by monomer contact and exposure to UV radiation has allowed for sensitive and unaided visual detection of the biotinylated DNA sequences. In effort to further reduce the detection limits and provide milder assay conditions, a second amplification system that relies on coupling visible light photoinitiators to a biochip surface and that is capable of polymerizing monomers that fluoresce has also been developed. Such a system has been used to achieve the unaided visual detection of complementary nucleic acid hybridizations of the K-Ras biomarker, whose known codon 12, 13 and 61 mutations have been shown to play a crucial role in the onset of several types of cancers, including lung, pancreatic, and colorectal cancer.