A novel MXene-integrated MIP-based electrochemical sensor for highly selective and sensitive lenalidomide recognition

A novel method for constructing a highly selective and sensitive MXene-supported electrochemical sensor based on MIP to detect Lenalidomide (LEN) is proposed in this study. The polymeric-coated layer was designed using ethylene glycol dimethacrylate (EGDMA) as the cross-linking agent, 2-hydroxyethyl methacrylate (HEMA) as the primary monomer, 2-hydroxy-2-methylpropiophenone as the photoinitiator, and 3-aminophenylboronic acid (3-APBA) as a functional monomer. 3-APBA introduces functional groups into the imprinting sites, facilitating specific interactions with the LEN molecule and enhancing the molecularly imprinted polymer's attachment efficiency and specificity. Electrochemical techniques, including Differential pulse voltammetry (DPV), Cyclic voltammetry (CV), and electrochemical impedance spectroscopy (EIS), were employed to investigate the behaviour of the designed MIP sensor at different stages: unmodified electrode, following photo-polymerization, after removal, and rebinding processes. Moreover, the morphological characterization was performed by scanning electron microscopy (SEM) to assess the surface characteristics of the fabricated sensor. The photopolymerization (PP) technique was used to develop the 3-APBA-LEN@β-CD-Ti₃C₂T_x/MIP-GCE sensor; the polymer solution was polymerized on the electrode surface under UV light (365 nm). Under optimal conditions, the fabricated sensor could determine LEN in standard solutions with a linear range of 1.75 × 10^-12 - 2.5 × 10^-11 M. The limit of detection (LOD) and limit of quantification (LOQ) for standard solutions were 4.21 × 10^-13 and 1.40 × 10^-12 M, respectively. For commercial serum, pharmaceutical dosage, and tap water, the recovery ratios were calculated as 99.07%, 97.88%, and 99.12%, respectively, with mean relative standard deviations (RSDs) below 2.0%. Furthermore, in the presence of LEN analogs and other interferences, the 3-APBA-LEN@β-CD-Ti₃C₂T_x/MIP-GCE demonstrated exceptional sensitivity and selectivity for LEN quantification. Moreover, the signal amplification mechanism of the engineered sensor was theoretically validated through Monte Carlo-based computational simulations. Structural modeling revealed that the β-cyclodextrin (β-CD) modifier acts as a highly effective molecular trap, forming a stable host-guest inclusion functionalized MXene-LEN. This robust thermodynamic affinity and mutual structural accommodation facilitate a powerful pre-concentration effect directly at the electrode-electrolyte interface. Consequently, this specific target entrapment fundamentally explains the enhanced sensitivity and superior electrochemical performance of the functionalized MXene platform.