High throughput prion assays

A method for preparing a biological sample suspected of containing PrPsc such that it is suitable for specific detection of PrPsc, said method comprising the steps of:

• homogenizing the sample using spherical beads, wherein each bead weighs between 50 mg and 100 mg;
• transferring a liquid fraction of the homogenate to a microwell plate, wherein said microwell plate comprises a coating of chaotropic agent, the coating comprising a mixture of a pre-determined amount of a chaotropic agent to partially denature PrPsc and water-soluble carbohydrate dried onto the interior surfaces of each well;
• digesting the homogenated fraction in the microwell plate with proteinase K, whereby PrPc present in the sample is digested and PrPsc present in the sample is partially digested but wherein a protease-resistant fragment of PrPsc present in the sample remains folded and undigested;
• and
• adding an unfolding reagent comprising a peptidic protease inhibitor to inhibit protease K activity and additional chaotropic agent to the digested homogenated fraction, wherein the additional chaotropic agent is guanidine hydrochloride and whereby the additional chaotropic agent achieves a final concentration of chaotropic agent sufficient to unfold the fragments of protease-resistant PrPsc present in the sample, thereby obtaining a biological sample suitable for specific detection of PrPsc.