Statistical Design of Experiments for Screening Influential Factors in Cold Atmospheric Plasma Processing of Chemical and Biological Functional Liquids Mixed via Single Bubble Rise: Terephthalic Acid as a Case Study

Cold atmospheric plasma (CAP) processing of chemical and biological functional liquids involves multiple interacting parameters that govern treatment uniformity and reactivity. Traditionally, a trial-and-error one-factor-at-a-time approach has been used, which is both time-consuming and resource-intensive. Here, we demonstrate a more powerful strategy using the Plackett–Burman statistical design of experiments (DOE) to screen key factors, with terephthalic acid (TA) serving as a fluorescence probe for hydroxyl radical (•OH) generation. The response—the fluorescence difference between the top and bottom regions of treated TA solutions—quantified the inhomogeneity of CAP processing. Screening of nine factors revealed that applied voltage, frequency, gas flow rate, nozzle height, and exposure time significantly influence uniformity, while gas type, voltage waveform, pH, and TA concentration are non-significant within the tested range. This DOE-based approach provides a systematic, cost-efficient pathway to optimize CAP treatment of functional liquids. Future studies will apply response-surface methodology to optimize bubble-mixing CAP for enhanced liquid uniformity.