Abstract: A microwell assembly that includes a tray that supports well inserts. The tray has an array of cylindrical cavities, each having an optically opaque cylindrical wall and an open base. The well inserts have wells having an optically clear bottom (e.g., a flat bottom, or a bottom of another geometry). The cylindrical cavities are sized to receive the well inserts such that the bottom of the wells does not extend beyond the cylindrical walls of the cavities. The opaque walls of the tray optically isolates the wells. In one embodiment, the entire structure of the well insert is economically made of the same material such as clear polymer. The tray may be reusable, and the well inserts are disposable. In one embodiment, the well insert may be configured in the form of a multi-well strip that includes wells at a spacing conforming to the inter-well spacing of a standard microplate.