Chromatographic techniques, renowned for their unparalleled separation resolution and detection sensitivity, have emerged as the gold-standard tool for the analysis and detection of chemical contaminants in various fields such as food safety and environmental pollution [1,2]. However, the inherent complexity of real-world sample matrices and the diversity of interfering substances pose significant challenges to analytical accuracy. This contradiction has driven continuous innovation in sample pretreatment technologies [[3], [4], [5]], among which magnetic solid-phase extraction (MSPE) demonstrates revolutionary potential in complex sample purification through its unique magnetic response separation mechanism, efficient mass transfer kinetics, and exceptional adsorption capacity [6,7]. Central to this technology are superparamagnetic nanoparticles (e.g., Fe₃O₄/γ-Fe₂O₃), which serve as the matrix. To achieve the high selectivity required for complex samples, specific recognition interfaces are constructed on these nanoparticles via surface modification. Aptamers, screened via Systematic Evolution of Ligands by Exponential Enrichment (SELEX) technology, exhibit nanomolar-level affinity and physicochemical stability, making them a new generation of biorecognition elements substituting traditional antibodies. Currently, aptamer-functionalized magnetic (apta-magnetic) sorbents have found successful applications in the selective separation of a diverse range of pollutants, including antibiotics [8], pesticides [9], toxins [10], heavy metals [11], and persistent organic pollutants [12].

Although the apta-magnetic sorbents exhibit excellent performance in terms of selectivity, stability, and operational convenience, the elution step still poses technical bottlenecks. Traditional elution methods rely on the use of organic solvents, such as ethanol [8,12,13] and methanol [9,10], to disrupt the non-covalent interactions between the aptamer and the target, which fundamentally conflicts with the green sustainable development paradigm of modern analytical chemistry. To address this contradiction, our team previously introduced the Strep-tag affinity system, enabling reversible aptamer-magnetic bead coupling through Strep-tag II/Strep-Tactin interaction [14]. This innovation facilitates target release under mild conditions (D-desthiobiotin competitive elution) and sorbent regeneration via NaOH treatment, maintaining analytical performance while significantly reducing environmental footprint. Nevertheless, the multi-step batch processing mode limits analytical throughput, and manual magnetic separation introduces operational errors, failing to meet high-throughput automated analysis demands.

The advent of microfluidic chip technology offers a novel approach to overcoming existing limitations. This technology operates by manipulating fluids at the microscale, integrating discrete laboratory operation units onto a centimeter-scale chip platform, thereby achieving miniaturization, automation, and intelligentization of analytical workflows. When microfluidic chips are combined with MSPE, a key issue that arises is the precise manipulation of sorbents within the microchannels. Currently, microfluidic MSPE predominantly employs two operational paradigms. The static mode immobilizes particles using microchannel confinement structures (e.g., nickel patterns [15], microcolumns [16,17], micro-hedges [18], and micropillar arrays [19]), offering operational stability but potentially limited efficiency due to constrained solid-liquid interfaces. Conversely, the dynamic mode disperses particles in flowing fluid, reducing diffusion paths [[20], [21], [22]] and enhancing collision frequency for improved target capture. However, keeping the particles evenly spread out in the flowing liquid (stable dispersion) is challenging, and designing microchannels that work reliably while allowing this free movement adds significant complexity. As a result, the dynamic approach, while promising, has seen less widespread use than the simpler static method.

To overcome these limitations, we have developed a new integrated microfluidic MSPE platform (Scheme 1). This platform is designed for the efficient extraction of acetamiprid, a widely used neonicotinoid pesticide [23]. The key to our design lies in two main parts working together: a mixing module and a magnetic separation module. Within the mixing module, a serpentine microchannel architecture induces dynamic fluid turbulence via chaotic advection, accelerating mass transfer between magnetic sorbents and analyte-laden samples. Crucially, to ensure the particles stay evenly dispersed, we use streptavidin-coated magnetic beads (SAMBs) instead of the previously used Strep-Tactin-coated beads (STMBs), as SAMBs offer better stability. These SAMBs are precisely modified on their surface with acetamiprid-binding aptamers (ABA) using a specific linking strategy (Strep-tag II) [24], enabling highly selective capture of acetamiprid. After capture, the bound acetamiprid can be gently released (eluted) using D-desthiobiotin, which binds much more weakly to streptavidin (Kd = 72 μM) [25] than biotin does (Kd = 10⁻¹⁴∼10⁻¹⁵ M). Following elution, acetamiprid is quantified via high-performance liquid chromatography (HPLC). This integrated system streamlines capture, separation, washing and elution within a single device, enabling operational automation and enhancing detection throughput.