Over recent decades, the quest for fast, efficient, and cost-effective extraction and analytical methods has gained significant attraction in both chemistry and engineering disciplines [1], [2], [3], [4]. Besides, environmental sustainability and responsible use of organic solvents have come under increased scrutiny, highlighting the need to minimize chemical consumption in extraction processes [5,6]. Introduced in 2006 [7], electro-membrane extraction (EME) has emerged as a versatile technique for extraction of various analytes from a wide range of biological, environmental, and wastewater samples [8], [9], [10]. Utilizing a voltage difference across a supported liquid membrane (SLM), EME facilitates the electrokinetic migration of charged analytes from the sample phase to an acceptor solution through the SLM [11]. Not only does this method require only a few microliters of solvent, making it a green alternative in liquid-liquid extraction procedures, but it also offers superior selectivity, purification, and sample cleanup due to rapid mass transfer [7,[11], [12], [13], [14]].

In the past decade, various EME formats have been introduced to develop the miniaturization techniques [7,[15], [16], [17]]. Utilizing miniaturized devices confers several advantages, such as reduced costs, quicker response times, enhanced automation, seamless integration, and minimized consumption of organic solvents and samples. These benefits collectively contribute to the development of more environmentally sustainable extraction procedures [17], [18], [19], [20], [21], [22]. Petersen et al. [23] introduced the first down-scaled EME setup on a microfluidic chip in 2010 [23]. Shortly after, numerous improvements with on-chip EME configurations were reported [13,[24], [25], [26], [27], [28]].

Zarghampour et al. [10] conducted a study on the EME of biogenic amines in food samples, achieving an adequate limit of detection (LOD) and repeatability [10]. In a subsequent publication, the same authors developed a chip capable of EME for both acidic and basic pharmaceuticals in a single device [26]. Diclofenac and nalmefene were chosen as the acidic and basic target analytes, respectively, yielding approximately 90 % recoveries in urine samples [26]. Santigosa et al. [11] successfully recovered over 78 % of five basic drugs with varying polarities from urine samples using a microfluidic device and a small 5 µLs of SLM [11]. Hidalgo et al. [27] enhanced the longevity of the SLM for the extraction of five drugs by utilizing two different polymethylmethacrylate (PMMA) chips. The authors achieved long-term stability (over 8 h) and approximately 94 % recoveries under optimal conditions [27]. Hansen et al. [29] demonstrated the first on-chip nanoliter-scale EME system, where six basic pharmaceuticals were extracted from 70 µL of urine, blood, and plasma samples. As a result of a high sample-to-acceptor volume proportion, enrichment factors of up to 400 after 60 min were obtained [29]. These findings highlight the significant and distinctive potential of microfluidic chips in EME applications.

The polymeric membrane support serves as an essential component in the EME process, influencing various parameters such as the stability of the SLM [30], phase interface effectiveness, phase interference and penetration, macromolecule and salt removal, mass transfer layer characteristics, and electrical resistance, which in turn affects the current passing through the SLM [11]. Despite its importance, there has been a notable gap in research concerning the impact of membrane morphology on extraction efficiency. Previous reports utilized commercial polypropylene (PP) or polyvinylidene fluoride (PVDF) membranes [11,14,22,31,32], which usually have different morphologies and properties due to various manufacturing methods and conditions [33,34].

In this study, PVDF flat membranes of varying pore sizes were fabricated to explore how their morphological characteristics influence the extraction of aspirin (ASA), naproxen (NAP), and ibuprofen (IBU) using an on-chip EME method. The non-solvent phase separation technique, a straightforward and cost-effective approach, was utilized to produce the PVDF membranes. These membranes were subsequently characterized using field-emission scanning electron microscopy (FESEM) and atomic force microscopy (AFM) to discern their morphological distinctions. To eliminate liquid leakages during the EME process, a silicone/PMMA microfluidic chip was utilized for the experiments, owing to excellent sealing properties of silicone. Additionally, silicone provides advantages such as flexibility, smooth channels, chemical and mechanical resistance, and cost-effectiveness. Furthermore, the impact of variables like acceptor phase composition, sample flow rate, and voltage on the enrichment factors (EF) of the drugs was evaluated and optimized.