The increasing global incidence of diabetes mellitus, driven by aging populations, sedentary lifestyles, and rising obesity rates, underscores the urgent demand for precise, reliable, and cost-effective glucose-monitoring technologies [1,2]. Accurate blood glucose measurements are essential for effective diabetes management and prevention of severe health complications [3–9]. Conventional enzymatic glucose sensors, primarily based on glucose oxidase (GOx), have been widely used because of their high selectivity. However, these enzyme-based systems have inherent drawbacks, including susceptibility to environmental fluctuations (such as temperature and pH), dependence on oxygen, limited operational stability, and relatively high production costs, which restrict their long-term practical applicability. Non-enzymatic electrochemical glucose sensors (NEGS) have emerged as a promising alternative technology for addressing these challenges, offering advantages such as enhanced robustness, lack of dependence on enzymatic activity, and low cost [10–13]. Recent advances have highlighted that NEGS, particularly those employing nanostructured transition-metal-based materials, demonstrate excellent electrocatalytic activity for glucose oxidation under diverse conditions. Among these, layered double hydroxides (LDHs), and particularly nickel-iron layered double hydroxides (NiFe-LDH), have attracted significant attention owing to their tunable layered structures, abundant electroactive sites, and intrinsic redox properties [14–19]. Nevertheless, pristine NiFe-LDH materials often exhibit moderate electrical conductivities and limited catalytic efficiencies, decreasing their sensing performance and hindering their practical use.

To overcome these limitations, doping strategies for the modulation of the electronic structure, defect chemistry, and electrocatalytic properties of LDH materials have been extensively explored [20–25]. Among various dopants, vanadium (V) has emerged as a particularly promising candidate due to its unique ability to enhance electron transport, create oxygen vacancies, and increase the redox flexibility of the LDH matrix [26–30]. The introduction of V into LDHs has been demonstrated to effectively modify the local coordination environment of the transition-metal sites, leading to enhanced electronic coupling between Ni, Fe, and V through oxygen bridges in the layered structure. This modification facilitates efficient charge redistribution within the LDH lattice, promoting dynamic electron-transfer pathways critical for catalysis. Moreover, the presence of V with multiple oxidation states (V³⁺/V⁴⁺/V⁵⁺) introduces additional redox centers that expand the density of electroactive sites [31–35]. Furthermore, V incorporation can induce lattice distortion and generate oxygen vacancies, which are known to act as active sites for electrochemical reactions and facilitate the adsorption and activation of reactant molecules, such as glucose [33,36]. In particular, oxygen vacancies in electrochemical systems not only improve electronic conductivity by introducing mid-gap states but also serve as catalytically active sites by stabilizing intermediate species and lowering energy barriers. While these effects have been extensively investigated in areas such as water splitting and CO₂ reduction, they remain relatively underexplored in the context of non-enzymatic glucose sensing. This gap suggests a significant opportunity for advancing glucose sensor design through deliberate defect engineering strategies, such as vanadium-induced vacancy formation in LDH systems. These structural and electronic modifications collectively contribute to lowering the reaction overpotential, improving the charge carrier mobility, and accelerating the reaction kinetics in electrochemical processes. Therefore, the strategic incorporation of V into NiFe-LDHs is expected to play a key role in enhancing the electrocatalytic performance of non-enzymatic glucose sensors by providing a more conductive framework, increasing the number of active sites, and promoting efficient electron transfer during glucose oxidation. This approach offers a promising pathway for the development of robust and sensitive sensors that can operate reliably under diverse conditions, thereby addressing the limitations of the existing enzyme-based sensing systems.

Building on these insights, this study focuses on the rational design and precise optimization of V-doped NiFe-LDH (NiFe₁₋ₓVₓ-LDH, 0 ≤ x ≤ 0.5) nanostructures as efficient non-enzymatic glucose sensors. By system-atically tailoring the V content and fine-tuning the structural characteristics of NiFe-LDH by direct controlled hydrothermal synthesis on nickel foam substrates, we achieved uniform incorporation of V into the LDH framework. This controlled doping strategy finely tuned the lattice and electronic structures, giving rise to hierarchical nanostructures with enriched redox-active sites and improved charge-transport pathways that collectively facilitated efficient glucose oxidation kinetics. As a result, the optimized NiFe_0.6V_0.4-LDH electrodes demonstrated outstanding glucose sensing performance, characterized by a high sensitivity of 1.891 mA mM⁻¹ cm⁻², an extended linear detection range, a low detection limit of 2.228 μM, and excellent operational stability. This study underscores the key role of V doping in modulating the electronic structure and defect chemistry of NiFe-LDH, thereby enabling high-performance non-enzymatic glucose sensing. Moreover, it offers a valuable framework for the rational design of advanced electrocatalytic systems for clinical diagnostics and practical biomedical applications.

Fig. 1 shows the synthetic route and structural evolution of V-doped NiFe-layered double hydroxide (NiFe-LDH) electrodes grown directly on nickel foam. As schematically shown in Fig. 1a, the pristine and V-doped NiFe-LDH electrodes were synthesized via a hydrothermal process in which nickel foam was immersed in a precursor solution containing Ni(NO₃)₂·6H₂O, Fe(NO₃)₃·9H₂O, and VCl₃, followed by reaction at 120°C for 12 h. The V doping level was modulated by varying the Fe:V molar ratio in the precursor solution. The resulting electrodes retained the 3D porous scaffold of the nickel foam while facilitating the uniform in situ growth of the LDH nanostructure.

The crystalline structures of the samples were investigated by X-ray diffraction (XRD), as shown in Fig. 1b. Both the pristine and V-doped NiFe-LDH samples displayed prominent diffraction peaks indexed to the (003), (006), (012), (015), (018), (110), and (113) planes, which are consistent with the characteristic rhombohedral LDH phase (PDF# 40-0125), indicating the preservation of the layered structure after V incorporation [37,38]. The substrate peaks at 44.5°, 51.8°, and 76.4° correspond to metallic Ni (PDF # 40-0125) from the underlying nickel foam. Notably, the (003) peak—commonly associated with the basal spacing and interlayer distance—exhibited a slight but discernible shift toward higher 2θ values upon V doping. A similar shift was observed for the (015) peak, which underwent a more pronounced rightward shift, indicating increased local distortion and lattice strain. This shift suggests a contraction in the interlayer height, which may be attributed to the smaller ionic radius of the dopant cations (V⁴⁺: 0.58 Å; V⁵⁺: 0.54 Å) replacing the Fe³⁺ (0.645 Å) ions. Such lattice distortions are accompanied by charge redistribution within the layered framework, which in turn modulates the electronic structure and enhances redox activity.

Morphological evolution upon vanadium incorporation was examined using field-emission scanning electron microscopy (FE-SEM) and high-resolution transmission electron microscopy (HR-TEM). As shown in Fig. 1c, the pristine NiFe-LDH electrode displays an assembly of nanosheets with a hierarchical organization. By contrast, the V-doped NiFe-LDH sample (Fig. 1d) exhibited a well-defined microflower-like morphology composed of densely packed and radially oriented ultrathin nanosheets. This morphological transformation is significant because such hierarchical structures are advantageous for enhancing electrolyte access, ion diffusion, and the electrochemically active surface area (ECSA). Furthermore, examination of the HR-TEM images provided further structural insights. As shown in Fig. 1e, pristine NiFe-LDH exhibited a clear lattice fringe spacing of 0.230 nm, corresponding to the (015) plane. Upon vanadium doping (Fig. 1f), this value decreased slightly to 0.228 nm, corroborating the lattice contraction deduced from the XRD results. This consistent d-spacing reduction confirms the successful incorporation of smaller vanadium ions into the LDH lattice and suggests an alteration in the local electronic environment, which may affect the redox behavior of the surrounding transition metal centers. Energy-dispersive X-ray spectroscopy (EDS) mapping was performed to evaluate the elemental distribution and compositional uniformity (Figs. 1g and 1h). The pristine NiFe-LDH showed a homogeneous distribution of Ni and Fe, whereas the V-doped sample exhibited a uniform dispersion of Ni, Fe, and V throughout the hierarchical nanostructure. The absence of elemental segregation and phase separation further validates the successful substitutional doping of vanadium into the LDH matrix. Taken together, these structural and morphological analyses confirm that V doping results in lattice contraction, hierarchical architecture formation, and increased structural disorder. These characteristics are expected to modulate the local electronic configuration and defect chemistry, which play key roles in determining the electrochemical performance. Moreover, the microflower-like morphology is anticipated to further accelerate glucose oxidation kinetics by facilitating electrolyte permeation and rapid glucose diffusion through its interconnected porous channels. The vertically aligned and cross-linked nanosheets act as efficient electron-transport pathways, minimizing charge-transfer resistance and promoting faster redox transitions at catalytically active Ni and V sites. Additionally, the mechanically stable hierarchical framework preserves the electrode integrity during prolonged electrochemical cycling, thereby ensuring reproducible and durable sensing performance [39–41]. Such morphological evolution is thus closely associated with the modulation of local electronic states and redox behavior of the LDH lattice. Building on these results, X-ray photoelectron spectroscopy (XPS) and electrochemical analysis were used to further probe how these structural modifications influence the redox state distribution, surface reactivity, and electrocatalytic activity toward glucose oxidation.

XPS measurements were performed to elucidate the electronic structure and oxidation states of NiFe₁₋ₓVₓ-LDH (0 ≤ x ≤ 0.5) electrodes, offering insights into the role of vanadium doping in modulating the redox behavior of the LDH catalyst. As shown in Fig. 2a, all samples exhibit characteristic Ni 2p peaks corresponding to Ni²⁺ (~855.6 eV) and Ni³⁺ (~857.2 eV), along with satellite features, confirming the coexistence of mixed valence states [37,38,42]. Notably, the relative intensity of the Ni³⁺ peak increases with increasing vanadium content and reaches its maximum in the NiFe_0.6V_0.4 composition. Such Ni³⁺ enrichment is particularly significant because high-valent Ni³⁺ species are well-established as catalytically active centers in alkaline glucose oxidation due to their enhanced electron-withdrawing capability and ability to promote faradaic charge transfer processes.

The successful incorporation of vanadium into the LDH matrix is verified by the V 2p spectra (Fig. 2b), which show well-defined peaks corresponding to both V⁴⁺ and V⁵⁺ oxidation states [28,30]. In particular, the presence of V⁵⁺ suggests a dynamic redox environment capable of participating in reversible electron exchange reactions during glucose oxidation. Moreover, these high-valent vanadium species promoted the formation of oxygen vacancies and electronic delocalization within the host lattice, thus contributing to improved charge transport and enhanced interfacial reactivity. To further correlate the oxidation state distribution with catalytic performance, the relative atomic percentages of Ni²⁺, Ni³⁺, and V⁵⁺ were evaluated through XPS peak deconvolution and are summarized in Fig. 2c. Among all compositions, NiFe_0.6V_0.4 exhibits the highest combined proportion of Ni³⁺ and V⁵⁺ species, indicating an optimized redox environment that is highly conducive to rapid electron transfer and favorable reaction kinetics. By contrast, excessive vanadium doping at x = 0.5 results in a decrease in both Ni³⁺ and V⁵⁺ content, likely due to lattice distortion and electronic oversaturation effects that destabilize high-valence states. These findings emphasize the importance of the precise control of V doping for achieving an optimal balance of redox activity, structural integrity, and electrical conductivity within the LDH framework.

As discussed in prior reports, the incorporation of high-valent transition metal ions, particularly V⁵⁺ and Ni³⁺, has emerged as a key strategy for enhancing electrocatalytic activity by facilitating multivalent redox cycling and lowering the energetic barrier for electrochemical reactions [39–41]. Such high-valence species introduce additional faradaic reaction pathways and serve as electronic bridges that enable efficient charge redistribution among the metal centers, thereby improving the intrinsic catalytic efficiency. Moreover, the ability of V⁵⁺ to stabilize oxygen vacancies further amplifies its role as a structural promoter of active sites, accelerating reaction kinetics and enhancing adsorption of glucose molecules [30,43–45]. Complementing vanadium incorporation, the increased proportion of Ni³⁺ within the LDH lattice also plays a key role in determining the electrochemical performance [45]. High-valent metal centers serve as strong electron acceptors, promoting the faradaic oxidation of glucose under alkaline conditions. Furthermore, the coexistence of these cations promotes structural stability and optimizes the defect environment, providing additional catalytic sites that facilitate glucose adsorption and activation. Collectively, the engineered redox environment—characterized by enriched Ni³⁺/V⁵⁺ content and structural defects—strongly enhances charge transfer efficiency, reduces the overpotential, and improves both sensitivity and stability in LDH-based non-enzymatic glucose sensors.

To gain deeper insight into the role of vanadium doping in modulating the defect chemistry of NiFe₁₋ₓVₓ-LDH (0 ≤ x ≤ 0.5), O 1s XPS spectra were acquired and analyzed to probe the evolution of oxygen-related species. As shown in Fig. 3a, a distinct peak centered at approximately 532.5 eV is observed, corresponding to oxygen-vacancy-related oxygen (Vₒ) species [26,28]. This feature reflects the formation of non-stoichiometric oxygen environments arising from charge-compensation mechanisms, wherein the incorporation of heterovalent V⁵⁺ ions into the LDH lattice induces local electronic imbalance and structural distortion. As shown in Fig. 3b, the relative intensity of the Vₒ component progressively increases with vanadium content, reaching a maximum for NiFe₀.₆V₀.₄-LDH, followed by a slight decrease at higher V concentrations. At the highest vanadium level (x = 0.5), the O 1s XPS spectra exhibit a reduction in the Vₒ fraction compared with x = 0.4, suggesting defect oversaturation and local structural instability. Together with the lattice-contraction behavior and mild peak broadening observed in the XRD patterns, these results indicate that excessive V incorporation induces lattice strain, which impairs electron mobility and charge-transfer efficiency, ultimately leading to diminished catalytic activity. Collectively, the XPS results reveal that moderate vanadium doping optimizes oxygen-vacancy generation and concurrently increases the concentrations of Ni³⁺ and V⁵⁺ species, thereby constructing a redox-active and electronically conductive surface microenvironment. Such controlled defect engineering enhances glucose adsorption and interfacial charge transfer [24,26], ultimately promoting efficient glucose electrooxidation. These findings underscore the pivotal role of vanadium-induced oxygen-vacancy formation in governing the electrochemical behavior of NiFe₁₋ₓVₓ-LDHs.

To further evaluate the glucose sensing capabilities of vanadium-doped NiFe₁₋ₓVₓ-LDH electrodes, amperometry and cyclic voltammetry analyses were performed. Fig. 4a presents the amperometric responses of the electrodes upon successive additions of glucose into 0.1 M KOH at an applied potential of 0.5 V vs. Ag/AgCl. A well-defined stepwise increase in the current is observed for all samples, with the NiFe_0.6V_0.4-LDH electrode exhibiting the highest current response throughout the tested concentration range. The stable baseline and reproducible stepwise current increments observed in the amperometric i–t curves (Fig. 4a) for NiFe₁₋ₓVₓ-LDHs further confirm the reliable signal stability and high signal-to-noise ratio of the sensor. By contrast, the pristine NiFe-LDH sample exhibited a much lower response, suggesting insufficient electrocatalytic activity. The pronounced improvement observed for the V-doped electrodes can be attributed to synergistic electronic and structural modifications, including increased Ni³⁺ content and oxygen vacancy concentration, which facilitate efficient glucose adsorption and subsequent oxidation via accelerated charge transfer kinetics. The corresponding calibration curves derived from the amperometry data (Fig. 4b) show a linear increase in the current density with increasing glucose concentration across all samples. The highest slope is observed for the NiFe_0.6V_0.4-LDH electrode, indicating its superior sensitivity and rapid response dynamics. This linear behavior (R² > 0.99) confirms the reliability and reproducibility of the sensing performance and reflects the stable electrochemical interface enabled by the hierarchical nanostructure and redox-active surface.

Fig. 4c quantitatively compares the sensitivities extracted from the linear fitting of Fig. 4b. The NiFe_0.6V_0.4-LDH electrode delivers the highest sensitivity of 1.324 mA mM⁻¹ cm⁻², while both under-doped and overdoped samples exhibit inferior values, suggesting the existence of an optimal doping concentration for maximizing electrochemical response. Notably, excessive vanadium content (e.g. x = 0.5) appeared to disrupt the redox balance and conductivity, as discussed above based on the XPS results. The inset in Fig. 4c shows cyclic voltammetry (CV) profiles acquired in the non-Faradaic region for ECSA estimation. The NiFe_0.6V_0.4-LDH sample exhibited the highest capacitive current, implying that it has the largest ECSA, showing a significant increase by a factor of 4.25 relative to the ECSA of the pristine NiFe-LDH. This morphological advantage, combined with the enhanced surface redox properties, enables a high density of accessible catalytic sites for glucose oxidation. Taken together, the electrochemical data presented in Fig. 4 show that the synergistic tuning of Ni and V valence states, coupled with hierarchical nanostructure formation and elevated oxygen vacancy content, significantly boosts the glucose oxidation activity. These enhancements gave rise to increased sensitivity, improved linearity, and robust signal stability, which are key parameters for practical non-enzymatic glucose-sensing platforms. From these comparative results, NiFe₀.₆V₀.₄-LDH was identified as the optimal composition exhibiting the highest sensitivity and most stable amperometric behavior among the series.

The glucose-sensing performance of this optimized electrode was further examined over an extended concentration range (0–5 mM) and compared directly with that of pristine NiFe-LDH to highlight the enhancement achieved through vanadium doping. As shown in Fig. 5a, the NiFe_0.6V_0.4-LDH electrode displays a well-defined, staircase-like increase in the current density upon successive glucose injections, demonstrating excellent signal resolution, repeatability, and rapid electrochemical response. The welldefined stepwise current increments and stable baseline observed during these successive glucose additions further demonstrate the reproducible and stable electrochemical behavior of the NiFe₀.₆V₀.₄–LDH electrode. Beyond this short-term behavior, vanadium incorporation is expected to play a key role in enhancing the long-term durability of the electrode. The lattice contraction and defect accommodation associated with V doping strengthen the LDH framework and suppress structural collapse, while the multivalent V⁴⁺/V⁵⁺ redox buffering stabilizes charge distribution and prevents over-oxidation of Ni sites during repetitive operation. Furthermore, the strong Ni–O–V interaction improves both electronic connectivity and structural integrity, enabling sustained charge transport and mechanical stability under continuous cycling. Nevertheless, during extended operation, partial V leaching or defect coalescence may still occur, progressively reducing the density of active sites and thus slightly diminishing catalytic efficiency. In future work, we plan to perform quantitative analyses of aging kinetics and vanadium leaching behavior to gain a deeper understanding of the long-term degradation mechanisms. Also, the magnified view shown in the inset of Fig. 5a highlights the sensor’s ability to detect ultra-low glucose concentrations down to 5 μM, with clearly distinguishable current steps for 5, 10, and 20 μM glucose additions. This sensitivity is particularly advantageous for early stage diabetes monitoring and hypoglycemic detection, where low-concentration accuracy is critical. The corresponding calibration plot (Fig. 5b) shows a strong linear correlation between the current density and glucose concentration up to 1.0 mM, yielding a correlation coefficient R² = 0.993. Beyond this range, a slight deviation from linearity is observed, likely due to catalytic site saturation or mass transfer limitations at higher analyte fluxes. Nevertheless, the current continues to increase with increasing concentration, confirming the broad detection capability of the electrode across the full 0–5.0 mM range. Based on the linear portion of the calibration curve, the NiFe_0.6V_0.4-LDH electrode achieves a high sensitivity of 1.891 mA mM⁻¹ cm⁻², markedly exceeding that of the undoped NiFe-LDH (0.674 mA mM⁻¹ cm⁻²). At higher glucose concentrations, a slight deviation from linearity is observed, which can be attributed to a mixed-control regime involving both surface coverage and mass-transfer limitations. As the reaction proceeds, the accumulation of glucose-derived intermediates progressively blocks the finite Ni³⁺/V⁵⁺ active sites, while the diffusion of glucose molecules through the electrolyte boundary layer becomes rate-determining, resulting in a sub-linear current increase at higher concentrations. Therefore, the sensitivity reported herein was extracted from the initial linear region (0–1 mM), while the extended range (1–5 mM) represents mixed-control kinetics consistent with previous studies on alkaline glucose oxidation [28,46-49]. Moreover, the limit of detection (LOD) for NiFe_0.6V_0.4-LDH, calculated based on a signal-to-noise ratio of 3, is estimated as 2.228 μM, significantly lower than the LOD of 3.443 μM obtained for the pristine electrode. Notably, as summarized in Table S1, the NiFe₀.₆V₀.₄-LDH exhibits superior electrochemical sensing performance to previously reported NiFe-based sensors with respect to both sensitivity and detection limit. These results clearly demonstrate that vanadium incorporation enhances electrochemical glucose sensing through synergistic modulation of valence states, defect structure, and hierarchical morphology, collectively improving charge transfer and catalytic efficiency (Fig. 5c). Beyond the increased Ni³⁺/V⁵⁺ ratio and high defect density, the superior electrochemical activity of NiFe₀.₆V₀.₄-LDH can be attributed to a synergistic multivalent electron-transfer pathway involving Ni, Fe, and V centers. Specifically, V⁵⁺ species may function as auxiliary redox mediators that either directly participate in glucose oxidation or facilitate rapid electron shuttling between neighboring Ni and Fe sites. This cooperative process, supported by overlapping redox potentials and the intimate atomic arrangement within the LDH lattice, significantly accelerates charge-transfer kinetics. Meanwhile, oxygen vacancies provide additional conductive channels and stabilize key intermediate species, collectively promoting efficient glucose oxidation. Thus, we believe that these modifications facilitate efficient electron transfer, increase the active surface area, and reduce kinetic barriers, thereby enabling highly sensitive non-enzymatic glucose detection over a wide range of concentrations.

In this study, we systematically demonstrate that vanadium doping is a highly effective strategy for modulating the structural and electronic properties of nickel-iron layered double hydroxide (NiFe-LDH) for high-performance non-enzymatic glucose sensing. Vanadium doping effectively tailors the lattice and defect structure of NiFe-LDH, promoting favorable Ni²⁺/Ni³⁺ and V⁴⁺/V⁵⁺ transitions that enhance charge transport and glucose oxidation activity. The optimized NiFe_0.6V_0.4-LDH electrode exhibited a high sensitivity of 1.891 mA mM⁻¹ cm⁻², a low detection limit of 2.228 μM, and wide linear response in the 0–5.0 mM range. Compared to the pristine NiFe-LDH, its V-doped counterpart achieved a 2.8-fold improvement in sensitivity and a lowering of the detection limit by ~35%. Moreover, the V-doped electrode displayed excellent operational stability and ultralow concentration resolution down to 5 μM. These findings highlight the synergistic interplay between redox-state regulation and defect engineering achieved through vanadium doping, providing a rational basis for the design of next-generation enzyme-free glucose sensors.