“…Several new formats, configurations, and extraction phases for EME have been introduced as of yet, namely, nanomaterial-assisted supported EME, gel-based supported EME, and EME with biodegradable membranes or green solvents (e.g., neoteric solvents), just to name a few. ,− Notwithstanding the widespread use of supported EME systems, some challenges still have to be faced to ameliorate the method’s repeatability because of the inability to precisely determine volumes of organic solvents embedded in the supporting phase and the nonuniformity of the polymer pores . In the meantime, there has been an increasing interest in accommodating supported EME in micro/millifluidic platforms with subsequent off-line/at-line liquid chromatography (LC)- or capillary electrophoresis (CE)-UV/mass spectrometric detection, , and in few instances with online detection. , The main issue of fluidic platforms accommodating supported EME that precludes method automation is the need for continuous regeneration of the liquid membrane because of the progressive washing out of the OP or the irreversible extraction of organic interfering compounds, whereupon the chip must be opened and the membrane replaced manually after every individual assay or sample batch. , To tackle this shortcoming, the concept of nonsupported micro-EME (μ-EME) with automatic regeneration of the organic phase by programmable flow in every single extraction without human intervention proved to be a superb alternative. , Unlike supported liquid membrane (SLM)-based EME, a plug of organic solvent is sandwiched between the DP and AP in μ-EME, mostly using perfluoroalkoxy and polytetrafluoroethylene (PTFE) tubings or pipet tips. , In μ-EME, phase formation can be readily automated with flow analysis so that varied and precise volumes can be used at will while increasing the stability and reliability with regard to the electrical current across EME and the extraction efficiency in complex real samples. , Despite the aforementioned advantages, single-line μ-EME bears significantly lower surface-to-volume ratios than those of standard SLMs; additionally, because the sample in μ-EME is stagnant, poor to moderate enrichment factors (EFs) are usually reported for μ-EMEs. Transfer of analytes might also potentially be hindered due to the accumulation of ions at the DP/OP and OP/AP interfaces, thereby resulting in reduced μ-EME recoveries and EFs of target ionizable analytes. , Therefore, there is a quest for designing and manufacturing novel fluidic platforms with intricate channel configurations enabling flexible handling of the DP, OP, and AP.…”