Cells of Escherichia coli were exposed to a downstream plasma afterglow plume emitted from a slotted plasma device operating in open air at atmospheric pressure. Various feed-gas mixtures were capacitively excited, as they flowed into open air past radio frequency-powered electrodes. To estimate the underlying inactivation pathways, various experimental conditions were tested by incorporating ultraviolet filters, varying parameters such as electrical power and frequency, feed-gas composition and flow rates, and the distance of the samples from the electrode. Experimental results demonstrated a colony-forming unit reduction of well over five logs with less than 2 s of exposure per unit area. These results offer a promising means of wide-area inactivation of harmful microbes in a practical environment, where the sample is neither a part of the electrical circuit nor placed in an enclosure. The device is electrically grounded and could be held like a wand applicator