At present, there are no efficient antemortem diagnostic tests for transmissible spongiform encephalopathys (TSEs), particularly in blood. New strains of prion PrPSc, which causes TSEs, are currently appearing, and researchers remain concerned that if prion variants continue to emerge, some of them may escape detection by existing immunoassay tests. Because a common structural feature of PrPSc strains is their high content of beta sheets, Raman spectroscopy has proven to be a suitable technique to analyze a key membranous fraction of blood containing PrPSc. In this fraction, a significant increase in beta sheets has been correlated with the worsening of this TSE in naturally scrapie-infected animals in comparison with healthy controls. Since sensitivity and specificity were found to be 100% for each, this test may lead to a new and alternative diagnosis for prion diseases.