Highly organized supercrystals of Au nanorods with plasmonic antennae enhancement of electrical field have made possible fast direct detection of prions in complex biological media such as serum and blood. The nearly perfect three-dimensional organization of nanorods render these systems excellent surface enhanced Raman scattering spectroscopy substrates with uniform electric field enhancement, leading to reproducibly high enhancement factor in the desirable spectral range.S urface enhanced Raman scattering (SERS) spectroscopy is not only one of the most sensitive analytical techniques but also can be used under biological conditions. Additionally, SERS signals are strongly dependent on conformational changes in macromolecules such as proteins (1). Unfortunately, although SERS of proteins has been consistently investigated during the last decade (2-6), enhancement factors (EFs) obtained for most conventional (nonfluorescent) proteins are still insufficient for their direct detection in complex biological media (7). There are two additional very serious challenges as well. Both quantitative detection by SERS and reproducible geometry of the "hot spots" necessary for SERS are difficult to achieve. The way to solve these challenges is to design and fabricate a highly organized photonic structure (8) that provides a high electromagnetic field enhancement in a reproducible geometry (9, 10). Recent demonstration of near-field focalization by nanoantennas (11,12) has paved the way for development of ultrasensitive SERS substrates that can concentrate the near field within certain confined regions, allowing one to obtain extremely high EFs (13-15). Such a nanoantenna effect was predicted and found for nanorod (NR) dimers, where the maximum focalization is present at the NR tips (16,17). One can hypothesize, therefore, that a highly organized system of NRs (18-21) acting as an extended nanoantenna may provide resolution for the SERS challenges of proteins or their segments. In turn, this hypothesis can lead to significant technological development for relevant biomedical problems. One example of those problems is the presymptomatic detection of scrambled prions directly in biological fluids.Prions are hard-to-detect infectious agents that cause a number of fatal neurodegenerative diseases in mammalians such as bovine spongiform encephalopathy (BSE), scrapie of sheep, and Creutzfeldt-Jakob disease (CJD) of humans (22), and recently traced as well to other neurodegenerative syndromes as Alzheimer's (23) and Parkinson (24). Invariably, all of these diseases involve the modification of the endogenous and functional prion protein (PrP C ) into a nonfunctional but much more stable form (PrP SC ) giving rise to the so-called amyloid plaques in the brain and other nervous tissues (25). Detection of its presence for contention in cattle or diagnosis in humans or blood transfusion banks (26) is very difficult even by state-of-the-art immunological methods such as fluorescence immunoassay, RIA, or ELISA (27) or protein misfolding c...