The formula most often used is attributed to Spearman and Kärber. In particular, how does one determine the standard error around one’s estimate of the median infectious dose (ID 50) or median seeding dose (SD 50), and how can one tell if two estimates from two different experiments are statistically different? But though I’ve used this method several times and have read papers that used it hundreds of times, I recently realized that I actually had no understanding of what the greater mathematical reasoning behind this method is. Intuitively, the logic employed is obvious: if you can dilute a sample 10 -8 and still cause disease in an animal, or a positive replicate in RT-QuIC, then there must have been 10 8 prions in the original undiluted sample. It’s used both in bioassay, where the quantity derived is called an “infectious unit” or “infectious dose”, and in RT-QuIC, where the quantity is called a “seeding unit”. In the study of prions, endpoint titration (also known as endpoint dilution) is a bread-and-butter method for quantifying the number of prions in a sample.
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