Approaches for assessing misfolding during therapeutic protein production are needed because such changes can expose potentially reactive epitopes, which can result in dangerous side effects. Antibodies to detect subtle protein conformation are difficult to obtain and there are not many tools to readily and routinely assess overall confirmation integrity. A group of authors from the US Food and Drug Administration show that aptamers may be able to detect minor conformational changes that are not detected by antibodies. The authors used enzyme-linked immunosorbent assays and label-free assays to assess the ability of four monoclonal antibodies and six aptamers to detect human thrombin that had been heat treated to perturb its structure without compromising its function. Whereas the panel of antibodies bound heat-treated and untreated thrombin equally well, some of the aptamers could discriminate between the two. Unlike monoclonal antibodies, which are time consuming and expensive to produce, aptamers are made using an in vitro selection process, greatly simplifying the production of a panel of aptamers against any protein. Aptamer panels may also be useful for assessing biosimilars. (PLoS ONE 7, e31948, 2012)