in combination with recently developed mabs against prp. the method of the present version of sofia provides sensitivity levels sufficient to detect prpsc in brain tissue. when coupled with limited spmca, the methods of the present inventions provide sensitivity levels sufficient to detect prpsc in blood plasma, tissue and other fluids collected antemortem. the methods combine the specificity of the mabs for antigen capture and concentration with the sensitivity of a surround optical fiber detection technology. in contrast to previously described methods for detection of prpsc in brain homogenates, these techniques, when used to study brain homogenates, do not use seeded polymerization, amplification, or enzymatic digestion (for example, by proteinase k, or “pk”). this is important in that previous reports have indicated the existence of prpsc isoforms with varied pk sensitivity, which decreases reliability of the assay. the sensitivity of this assay makes it suitable as a platform for rapid prion detection assay in biological fluids. in addition to prion diseases, the method may provide a means for rapid, high-throughput testing for a wide spectrum of infections and disorders. while about 40 cycles of spmca combined with immunoprecipitation were found to be inadequate for prpsc detection in plasma by elisa or western blotting, the prpsc has also been found to be readily measured by sofia methods. the limited numbers of cycles necessary for the present assay platform virtually eliminates the possibility of obtaining pmca-related false-positive results such as those previously reported (thorne and terry, 2008). other clinical applications with rapid developments in the field of biomarker research, many infections and disorders that have not been possible to diagnose via in vitro testing, are becoming increasingly possible. sofia is predicted to be of broader use in diagnostic assay development for infections and disorders beyond the scope of prion diseases. a major potential application is for other protein misfolding diseases, in particular alzheimer's. published research a 2011 study reported the detection of prions in urine from naturally and orally infected sheep with clinical scrapie agent and orally infected preclinical and infected white-tailed deer with clinical chronic wasting disease (cwd). this is the first report on prion detection of prpsc from the urine of naturally or preclinical prion-diseased ovines or cervids. a 2010 study demonstrated a moderate amount of protein misfolding cyclic amplification (pmca) coupled to a novel sofia detection scheme, can be used to detect prpsc in protease-untreated plasma from preclinical and clinical scrapie sheep, and white-tailed deer with chronic wasting disease, following natural and experimental infection. the disease-associated form of the prion protein (prpsc), resulting from a conformational change of the normal (cellular) form of prion protein (prpc), is considered central to neuropathogenesis and serves as the only reliable molecular marker for prion disease diagnosis. while the highest levels of prpsc are present in the cns, the development of a reasonable diagnostic assay requires the use of body fluids which characteristically contains extremely low levels of prpsc. prpsc has been detected in the blood of sick animals by means of pmca technology. however, repeated cycling over several days, which is necessary for pmca of blood material, has been reported to result in decreased specificity (false positives). to generate an assay for prpsc in blood that is both highly sensitive and specific, the researchers used limited serial pmca (spmca) with sofia. they did not find any enhancement of spmca with the addition of polyadenylic acid, nor was it necessary to match the genotypes of the prpc and prpsc sources for efficient amplification. a 2009 study found sofia, in its current format, is capable of detecting less than 10 attogram (ag) of hamster, sheep and deer recombinant prp. about 10 ag of prpsc from 263k-infected hamster brains can be detected with similar lower limits of prpsc detection from the brains of scrapie-infected sheep and deer infected with chronic wasting disease. these detection limits allow protease-treated and untreated material to be diluted beyond the point where prpc, nonspecific proteins or other extraneous material may interfere with prpsc signal detection and/or specificity. this not only eliminates the issue of specificity of prpsc detection, but also increases sensitivity, since the possibility of partial prpsc proteolysis is no longer a concern. sofia will likely lead to early ante mortem detection of transmissible encephalopathies and is also amenable for use with additional target amplification protocols. sofia represents a sensitive means for detecting specific proteins involved in disease pathogenesis and/or diagnosis that extends beyond the scope of the transmissible spongiform encephalopathies.