The use of in situtransmission electron microscopy (TEM) to study biological processes is a new frontier in high-resolution imaging. Here we report the development of affinity capture devices that are used to isolate biological entities for in situ studies. Affinity capture devices are silicon nitride microchips coated with functionalized lipid monolayers. We tested the isolation capacity of the devices by using protein synthesis machinery as a test specimen for single particle and in situTEM analysis. Overall, we demonstrate the feasibility of purifying biological assemblies in a liquid environment within a TEM column. This novel application may serve to bridge the gap between cellular and molecular imaging techniques.