How are “interesting” research problems identified and made durable by academic researchers, particularly in situations defined by multiple evaluation principles? Building on two case studies of research groups working on rare diseases in academic biomedicine, we explore how group leaders arrange their groups to encompass research problems that latch onto distinct evaluation principles by dividing and combining work into “basic-oriented” and “clinical-oriented” spheres of inquiry. Following recent developments in the sociology of valuation comparing academics to capitalist entrepreneurs in pursuit of (...) varying kinds of worth, we argue that the metaphor of the portfolio is helpful in analyzing how group leaders manage these different research lines as “alternative investment options” from which they were variously hoping to capitalize. We argue portfolio development is a useful concept for exploring how group leaders fashion “entrepreneurial” practices to manage and exploit tensions between multiple matrices of valuation and conclude with suggestions for how this vocabulary can further extend analysis of epistemic capitalism within science and technology studies. (shrink)