Protein flocculation is a major concern for protein therapeutics produced by the biotechnology industry. Protein flocculation can occur after freezing or long-term storage, which can lead to a decrease in treatment efficacy. More insidiously, flocculated proteins have been reported to induce immunogenicity—a significant safety concern. Despite the importance of simple and accurate techniques to quantify flocculation, challenges remain. Here we describe a new method to detect the degree of flocculation, namely, electrospray-differential mobility analysis (ES-DMA), also known as gas-phase electrophoretic mobility molecular analysis (GEMMA). ES-DMA uses electrospray to convey proteins, protein aggregates and self-assembled protein structures (i.e virus like particles) into the gas phase. Differential mobility analysis then separates the proteins based on their charge-to-drag ratio, after which particles of a specific size are counted with a condensation particle counter. In this way a size distribution for particles ranging from antibodies and gold particles to virii may be obtained. We find this method best characterizes and quantifies the initial states of flocculation, particularly for dimers, trimers, and tetramers, and proteins with molecular weights in excess of 10 kDa.