1. Introduction

As the global community increasingly prioritizes health, environmental sustainability, and food safety, portable, highly sensitive, and rapid-response electrochemical sensors have emerged as a focal point of research, playing an indispensable role in environmental monitoring, medical diagnostics, and food safety assessments [1-4]. Favored for their miniaturization, cost-effectiveness, and exceptional sensitivity, electrochemical sensors are progressively outpacing traditional sensing technologies such as atomic emission spectroscopy (AES), chromatographic techniques, and inductively coupled plasma mass spectrometry (ICP-MS) [5,6]. Electrochemical sensors, by rapidly and accurately identifying analytes, can convert specific chemical or bio-chemical reactions into quantifiable electrical signals, thereby serving a critical function in monitoring and analysis tasks [7]. Hence, selecting suitable sensing materials is pivotal in the development of high-performance electrochemical sensors. Although traditional materials like metal oxides, carbon nanotubes, and conductive polymers have already demonstrated notable achievements in this domain, the exploration and development of novel, high-efficiency electrochemical sensing materials continue unabated [8-13].

Metal-organic frameworks (MOFs), also known as porous coordination polymers, represent a class of crystalline materials self-assembled from metal ions or clusters and organic ligands [14]. They are distinguished by their exceptionally high specific surface areas, tunable chemical compositions and structures, and high porosities. These attributes endow MOFs with tremendous potential for development in various applications such as gas storage, separation, catalysis, and drug delivery [15,16], while also broadening their applicability in the realm of sensing, including fluorescence sensing [17], colorimetric sensing [18], and electrochemical sensing [19]. Among these, the application of MOFs in electrochemical sensing has garnered particular attention due to the high sensitivity, outstanding selectivity, rapid detection capabilities, and low cost associated with electrochemical sensors [20,21]. For instance, Sakthivel et al. [22] successfully designed an apt sensor based on a Cu-BTC/ZIF-L [copper benzene-1,3,5-tricarboxylate (Cu-BTC)/zeolitic imidazolate framework-laminar (ZIF-L)] composite, achieving real-time detection of insulin in vivo; Wang et al. [23] constructed a Co-TMC4R-BDC electrochemical sensor for the capture and detection of heavy metal ions in aqueous solutions. However, most MOFs typically exhibit poor conductivity, which to a certain extent limits their application scope in the field of electrochemical sensing [24]. Therefore, the development of conductive metal-organic frameworks (CMOFs) with excellent conductivity has become key to advancing progress in this area. CMOFs are a class of crystalline materials composed of metal ions and organic ligands, exhibiting excellent conductive properties due to their unique structure and chemical composition. Compared to traditional MOFs, CMOFs enhance electrical conductivity by introducing conjugated organic ligands or conductive metal clusters, thereby facilitating electron transport. CMOFs can be categorized into electronic conductive and proton conductive types. The former relies on electron migration between the metal centers and organic ligands for conductivity, while the latter enhances proton conductivity by incorporating acidic groups or doping with proton conductors. Their efficient carrier transport mechanisms are realized through π-π stacking or π-d conjugation structures, and the carrier transfer pathways are further strengthened by spatial and valence bond interactions [25,26].

In recent years, to overcome the barrier of poor conductivity in most MOFs, researchers have successfully synthesized a variety of novel CMOFs through meticulous design and functionalization strategies [25]. These CMOFs combine the unique porous characteristics of MOFs with enhanced electrical conductivity, significantly expanding the potential applications of MOFs in the field of electrochemical sensing [26]. CMOFs, as materials with the promise to revolutionize the electrochemical sensing platform, boast several key advantages: (1) CMOFs possess unsaturated metal coordination sites and unique structural benefits, including large surface areas and adjustable porosity and structural morphologies, endowing them with superior catalytic capabilities. This makes them suitable as efficient coatings for electrocatalytic electrodes in electrochemical sensors. (2) The high porosity and large surface area of CMOFs facilitate the efficient adsorption and enrichment of analytes, thereby effectively enhancing signal response and improving the sensitivity of the sensors. (3) The pore size and morphology of CMOFs can be designed for targeted selectivity, achieving exceptional analyte recognition performance through size-exclusion effects and specific interactions with analytes. (4) CMOFs inherit many advantages of traditional MOFs and endow them with excellent electronic conductivity, exhibiting outstanding performance characteristics in the field of electrochemical sensors [6,27,28]. Currently, research on the application of CMOFs in electrochemical sensing is rapidly evolving and is expected to revolutionize the field of sensing technology. At present, there is still a relatively limited amount of literature on the application of CMOFs in electrochemical sensing, and comprehensive research reviews have not yet been established. This article aims to organize and discuss the research progress of CMOFs in the application of electrochemical sensing, covering their synthesis strategies, functionalization pathways, and case studies in various types of sensing applications. Ultimately, the article will provide an outlook on the challenges and issues faced by CMOFs-based electrochemical sensors, offering guidance for future research directions (Scheme 1).

2. Synthesis of CMOFs

The design principles of CMOFs involve selecting organic ligands with π-π stacking, conjugated structures, or inherent conductivity, and combining them with corresponding metal centers. Organic ligands with these characteristics provide effective electron channels, forming continuous electron clouds that allow electrons to move freely between ligands, thereby enhancing conductivity. The coordination bonds formed between metal ions and organic ligands construct a stable framework structure, and selecting appropriate metal centers can optimize the framework's electronic structure, further enhancing conductivity. Introducing conjugated organic ligands or conductive metal clusters facilitates electron transport, providing efficient electron transmission pathways and reducing energy loss. For proton-conductive MOFs, incorporating acidic groups or doping with proton conductors increase proton migration rates, forming a continuous proton transport network. These design principles help optimize the conductive performance of MOFs, making them excel in applications involving both electronic and proton conduction [17,27,28]. Currently, CMOFs used in electrochemical sensing can be classified into four main categories: Cu-based CMOFs, Ni-based CMOFs, and Fe-based CMOFs, with Cu-based CMOFs comprising the majority. The ligands for Cu-based CMOFs and Ni-based CMOFs are essentially identical (Fig. 1). Additionally, there are CMOF composites formed by combining with other materials such as carbonaceous materials, and noble metal nanoparticles.

2.1. Cu-based CMOFs

Cu-based CMOFs are primarily assembled from Cu²⁺ ions and various ligands with conjugated structures (2,3,6,7,10,11-hexahydroxytriphenylene (HHTP), 2,3,6,7,10,11-hexaamine triphenylene (HITP), tetrahydroxy-1, 4-benzoquinone (THQ), benzene hexathiol (BHT), etc.). In most cases, owing to well-overlapped spatial and energetic orbitals between the metal and ligand electronic orbitals, as well as their non-covalent interactions, Cu-based CMOFs inherently possess excellent conductivity. Currently, synthetic methodologies for Cu-based CMOFs mainly include hydrothermal/solvothermal method, interface-assisted synthesis, self-assembly, and spray-coating.

2.1.1. Hydrothermal/solvothermal method

Hydrothermal/solvothermal synthesis is one of the most common methods for synthesizing Cu-based CMOFs, involving high-temperature, high-pressure sealed reactions in autoclaves. This method not only enhances the solubility and reactivity of reactants but also improves crystallinity, providing favorable conditions for crystal growth. For instance, Hu et al. [29] successfully grew conductive Cu-MOFs on copper foam (CF) via a one-step hydrothermal/solvothermal method, using Cu nodes and HHTP ligands, which served as effective catalytic electrodes for electrochemical oxidation of glucose under alkaline conditions. Compared to HHTP ligands, THQ ligands form frameworks with smaller pore sizes, increasing the redox-active sites in CMOFs assembled from metal nodes and THQ ligands. Niu et al. [30] synthesized three types of 2D CMOFs using hydrothermal/solvothermal methods, assembling metal nodes (Cu, Ni) with conjugated organic ligands (HHTP, THQ), namely Ni₃(HHTP)₂, Cu₃(HHTP)₂, and Cu₃(THQ)₂. Owing to the topological combination of square planar coordinated Ni²⁺ and Cu²⁺ with hexagonal ligands, all CMOFs exhibit a 2D hexagonal structure. The fabricated CMOFs, possessing negatively charged frameworks, opted for cationic probes such as (Ru(NH₃)₆³⁺ and methylene green. Among them, Cu₃(THQ)₂ showed the highest current response with (Ru(NH₃)₆³⁺ and the lowest with methylene green. This discrepancy is attributed to the larger-sized methylene green probes (~1.3 nm), which struggle to reach the active sites within the smaller pore sizes of Cu₃(THQ)₂ (~1.1 nm), resulting in weaker current responses. In contrast, the larger pore sizes of Cu₃(HHTP)₂ and Ni₃(HHTP)₂ (~1.9 nm) facilitate more effective interaction with methylene green probes. Furthermore, the smaller pore-sized Cu₃(THQ)₂, with a greater specific surface area, hosts more redox-active sites, displaying exceptional electrocatalytic performance at lower potentials (0.39 V) based on Cu₃(THQ)₂ sensors (Fig. 2A). Electrical conductivity (σ) is a key parameter for evaluating the conductive performance of materials. The conductivity of CMOFs is determined by their composition and structure, but precise measurement remains challenging due to inherent properties and equipment limitations. Conductivity can be derived from ohm's law using the formula

$ \sigma=G \frac{L}{A}=\frac{I}{V} \times \frac{L}{A} $

(1)

where I is the current, V is the voltage, L is the length over which the voltage drops, G is electrical conductance and A is the cross-sectional area. The ratio of I to V can be measured using the two-probe or four-probe method. Conductivity is determined by the carrier density (n) and mobility (µ), as described by the formula

$ \sigma=e\left(\mu_{\mathrm{e}} n_{\mathrm{e}}+\mu_{\mathrm{h}} n_{\mathrm{h}}\right) $

(2)

where e represents electrons and h represents holes. Achieving high conductivity requires high charge density and good charge mobility. High charge density can come from free carriers in metallic conductors or thermally activated carriers in semiconductors. Constructing CMOFs requires meeting the following criteria: containing high-energy electrons or holes, stable free radicals, and providing unpaired electrons or molecules with redox activity to facilitate charge transfer between metal nodes. Currently, the electrical conductivity of many CMOFs is measured using I-V curves [24,25]. To date, ligands for CMOFs have predominantly relied on hexa-substituted benzene or triphenylene (e.g., HHTP), which harbor unavoidable limitations such as limited surface areas and lack of functional groups, curtailing the maximal potential of these materials. To overcome these challenges, Hoai et al. [31] synthesized a CMOF via hydrothermal/solvothermal method, assembling 2,3,8,9,14,15-hexahydroxytriphenylene (HHTC) ligands with Cu nodes, termed Cu₃(HHTC)₂. HHTC ligands, featuring six hydroxy groups and a fully conjugated structure, are topologically like HHTP. Theoretically, the inherent voids and larger size of HHTC allow for a CMOF with a larger surface area, with Cu₃(HHTC)₂ reaching a surface area of 1196 m²/g and an electrical conductivity of 3.02 × 10⁻³ S/cm. The electrical conductivity is determined through I-V curves. The pore size hierarchy among these three Cu-based CMOFs is: Cu₃(THQ)₂ < Cu₃(HHTP)₂ < Cu₃(HHTC)₂, noting the purification process of HHTC ligands is comparatively complex. Given most CMOFs are prepared as powders via hydrothermal/solvothermal methods, meeting the demands of practical applications poses a challenge. Thus, a pressing issue is the development and study of CMOFs films or textiles, aiming to broaden their application prospects in sensing and beyond.

2.1.2. Interface-assisted synthesis method

Utilizing interfaces such as liquid/liquid, liquid/gas, and solid/liquid as templates for the growth of Cu-based CMOFs films is a prevalent method for fabricating high-quality Cu-based CMOF films. The through-bond mechanism from a chemical perspective has become a crucial reference design principle for CMOFs. This mechanism relies on the formation of covalent bonds due to the matching energy levels between the metal and ligand. These continuous covalent interactions create an extensive conjugated system, resulting in delocalized electrons, thereby producing a narrower band gap and higher electron mobility. By adjusting the symmetry and overlap of the metal and ligand orbitals (such as forming π-d conjugated structures), the electron transfer process can be effectively regulated. The through-bond conduction mechanism facilitates charge transport by transmitting charge through continuous coordination or covalent bonds [26,28]. The density difference between two immiscible solvents results in layering, forming a liquid/liquid interface. Wu et al. [32] proposed that during the reaction process at a liquid/liquid interface, adjusting the proton concentration alone can generate metal vacancies to regulate BHT coordination polymer films. By controlling the self-assembly rate through pH adjustment, a series of coordination polymers with controllable metal vacancies (Cu-BHT, Ni-BHT, and Ag-BHT) were successfully fabricated. The BHT ligand, with its simple structure and six thiol groups linked to a benzene ring, allows for a fully π-d conjugated 2D monolayer plane with the transition metal center, thereby enhancing conductivity. Among these coordination polymers, Cu-BHT exhibited the best conductivity due to numerous Cu vacancies leading to structural defects such as reduced crystallinity, which, however, significantly improved electrocatalytic activity. The thickness of the Cu-BHT film was about 100 nm (Fig. 2B). The technique of forming a liquid/air interface has been applied to the synthesis of many ultrathin materials. Chen et al. [33] prepared even thinner Cu-BHT films (16 nm) using a liquid/air interface reaction method by diffusing BHT into an acidic aqueous solution of Cu(NO₃)₂ with a pH of 1 in air. Increasing the proton concentration can slow down the coordination reaction, improving the crystallinity of the Cu-BHT film. Observing the change in surface morphology with reaction time revealed that the Cu-BHT film grew directionally from top to bottom at the water/organic interface, and an almost transparent film could be seen floating on the water surface after the organic solvent evaporated. Unlike the synthesis of CMOFs via the liquid/liquid interface reaction method (mixing the ligand solution with the salt solution), the solid/liquid interface reaction method is also commonly used to prepare Cu-based CMOF films. This method involves the rapid transformation of solid ligands into CMOFs in a salt solution. Miao et al. [34] prepared TOM-Cu₃(HITP)₂ films using a solid/liquid reaction method where the HATP solid ligand with a three-dimensional ordered sub-micron porous (TOM) morphology instantaneously transformed into insoluble Cu₃(HITP)₂ MOF upon reacting with Cu²⁺. Due to the extremely fast coordination reaction speed, the initial three-dimensional ordered TOM morphology of the ligand was maintained during the transformation, achieving the synthesis of Cu₃(HITP)₂ MOF films with large-scale TOM morphology on ceramic-based interdigitated electrodes (IDEs). Compared to conventional Cu₃(HITP)₂ MOFs, TOM-Cu₃(HITP)₂ films have no essential difference in composition, except for slight variations in the content of certain surface functional groups and overall crystallinity. However, the introduction of the TOM structure endowed the TOM-Cu₃(HITP)₂ film with a hierarchical TOM microporous structure. The rich TOM microporous hierarchical structure exposed more active sites in the TOM-Cu₃(HITP)₂ film, greatly facilitating the mass transfer of gas molecules, thus significantly improving gas sensitivity. Despite the excellent conductivity, good crystallinity, thin thickness, and outstanding gas sensitivity performance of Cu-based CMOF films prepared by interface-assisted synthesis methods, controlling the thickness of the films remains a challenge. These issues primarily include: (1) Minor variations in reaction conditions during interface-assisted synthesis affect the uniformity of the film, necessitating systematic optimization of parameters such as temperature, time, and solvent concentration. (2) Uneven deposition rates lead to non-uniform thickness; thus, a stepwise deposition method should be employed to control the deposition rate and adjust the thickness layer by layer. (3) Interface stability affects film growth, requiring the use of stabilizers or surfactants to enhance stability. (4) Consistent reaction conditions are difficult to achieve during large-area preparation, so a closed or semi-closed environment should be used to control solvent evaporation. Addressing these issues can partially overcome the challenges of controlling film thickness, thereby improving the performance and reliability of Cu-based CMOFs films in practical applications [17].

2.1.3. Other synthesis methods

In addition to interface-assisted synthesis methods, spray-coating and self-assembly techniques have also been applied to the synthesis of Cu-based CMOFs films. The Layer-by-Layer (LbL) spray-coating liquid-phase epitaxy method allows for the controlled fabrication of Cu-based CMOF films in terms of thickness. For instance, Yao et al. [35] synthesized Cu₃(HHTP)₂ films assembled from Cu nodes and HHTP ligands via the LbL method, enabling controlled fabrication of the films. These Cu₃(HHTP)₂ films not only grew by ~2 nm per growth cycle but could also be precisely fabricated within a thickness range of 10–100 nm, featuring smooth surfaces, good crystallinity, and high orientation. Cu₃(HHTP)₂ films with a thickness of 20 nm exhibited excellent room-temperature sensing performance. Wu et al. [36] also utilized the LbL method to fabricate CMOF films. To further enhance the sensitivity and selectivity of the films, they designed a dual-ligand strategy, using two redox-active ligands with different coordinating groups (HHTP, -OH) and (HITP, -NH₂), to prepare HITP-doped Cu-HHTP-10C nanofilms. These nanofilms could be precisely fabricated within the nanoscale range (20–70 nm) and featured smooth, poreless surfaces. The mixed-framework significantly altered the electronic structure, thus the HITP-doped Cu-HHTP-10C nanofilms exhibited excellent sensitivity and selectivity towards different gases, and finely tuned the chemical resistive sensing performance of the nanofilms. The LbL method requires multiple distinct spraying steps and a considerable amount of time to grow the layers of the film, making the whole process tedious and time-consuming. Moreover, the thinnest Cu-based CMOF films prepared using the LbL method mentioned above have a thickness of about 10 nm, which cannot meet the demands for thinner films in devices. Chen et al. [37] proposed a spin-coating interface self-assembly method (SCIS), capable of rapidly synthesizing Cu-BHT MOFs films of centimeter size on various substrates (glass, Si, Si/SiO₂, and polyester substrates with pre-deposited gold electrodes). By controlling the reaction time from 5 s to 16 min, the thickness (5–35 nm) and surface morphology of Cu-BHT films could be precisely adjusted. Cu-BHT films with a 2D lattice structure exhibited excellent electrical conductivity of 2500 S/cm at room temperature, and the crystal particles induced on the film surface enhanced the sensing performance through Cu_2c sites (Fig. 2C). Considering the wide applications of CMOFs, the SCIS method for ultra-fast in-situ synthesis of large-area CMOF films on various substrates could have a significant technological impact. Therefore, further research on this method is necessary to ensure its widespread application in the sensing field.

The oxidative reassembly synthesis method can integrate CMOFs onto textiles. Eagleton et al. [38] used this method to convert zero-valent copper metal (Cu⁰) and HHTP ligand into Cu₃(HHTP)₂, then integrated Cu₃(HHTP)₂ into various flexible porous woven fabrics (cotton, silk, nylon, nylon/cotton blend, and polyester) and non-woven substrates to create conductive textile materials. The conductive textile materials exhibited resistances of 0.1–10.1 MΩ/cm² (depending on the substrate) and were capable of withstanding physical and chemical stresses such as abrasion and detergent washing. When integrating CMOFs onto textiles using the oxidative reassembly synthesis method, it featured five notable characteristics: (1) Controlled patterning on a square centimeter scale with micrometer resolution; (2) Universality across various types of substrates (such as cotton, silk, nylon, nylon/cotton blend, polyester, and non-woven fabrics); (3) Robustness of the prepared CMOF/textiles, capable of withstanding various forms of wear, thermal and chemical washing, while maintaining their chemical sensing performance; (4) The feasibility of the experiment in mild water conditions, meeting green chemistry process requirements; (5) Rapidity of the method. Although oxidative reassembly enables the convenient and functional integration of Cu₃(HHTP)₂ into textiles under ambient conditions, several limitations currently exist with this method. Firstly, studies on the metal-organic reassembly into CMOFs have been limited to Cu⁰ so far. Secondly, the method requires the use of a thermal evaporator, which limits the patterning of copper metal to planar processing and may be restrictive in terms of scalability. Lastly, current research demonstrations are limited to the HHTP ligand. To make this method more widely applicable, optimization of reaction conditions and other aspects is necessary to turn it into a technology for producing multifunctional electronic textiles.

2.2. Ni-based CMOFs

The synthesis methods for Ni-based CMOFs are similar to those of Cu-based CMOFs, including hydrothermal/solvothermal methods and interface-assisted synthesis techniques. CMOFs composed of benzene or triphenyl derivative ligands, which possess adjacent di-substituted N, O, or S atoms, ensure electron transfer due to their highly conjugated and delocalized π bonds, thereby enhancing conductivity. Consequently, Qiao et al. [39] synthesized a 3D conjugated CMOF, Ni₃(HHTP)₂, composed of nickel salts and HHTP ligands using the hydrothermal/solvothermal method. This material had a specific surface area of 12.1467 m²/g, with pore sizes primarily distributed in the 2–9 nm range. Additionally, Wang et al. [40] hydrothermally/solvothermally synthesized conductive Ni₃(HITP)₂ nanorods with higher crystallinity using Ni²⁺ and HITP ligands. Due to the synergistic action of highly active Ni-N₄ catalytic sites in the nanorods, along with a 2D stacked honeycomb lattice and a large specific surface area of 548.2 m²/g (average pore size approximately 1.3 nm), these facilitated efficient electron transfer, enhancing conductivity. Compared to Ni₃(HHTP)₂, Ni₃(HITP)₂ has a larger specific surface area and smaller pore sizes. Thus, Ni₃(HITP)₂ contains numerous internal pore channels, increasing the contact area between the catalyst and the electrolyte, and providing effective ion transport during the electrocatalytic oxidation of the analyte. However, it has been reported that direct growth of Ni₃(HITP)₂ films on solid substrates or precipitation from solution surfaces using hydrothermal/solvothermal methods poorly controls film growth. The obtained Ni₃(HITP)₂ films are relatively thick (~500 nm), lack preferred orientation, and exhibit poor uniformity. Therefore, Ohata et al. [41] adopted a liquid/gas interface synthesis method to prepare CMOF nanosheets. HATP solution was diffused onto an aqueous solution of Ni(OAc)₂•4H₂O, and deprotonated HATP (HITP) reacted with Ni²⁺ at the liquid/air interface to immediately form CMOF nanosheets (HITP-Ni-NS). These nanosheets have a multilayer structure of 14 nm thickness, high crystallinity, and uniaxial orientation, easily transferable to any desired substrate, with an electrical conductivity of 0.6 S/cm (Fig. 3A). To date, most reports on Ni₃(HITP)₂ films have been prepared on bare substrates using hydrothermal/solvothermal methods or interface-assisted synthesis. However, these methods present certain complexities in fabricating Ni₃(HITP)₂ films amenable to large-area formation, limiting their feasibility in various applications. To address these challenges, Lee et al. [42] proposed a microfluidic-assisted solution shearing combined with post rapid crystallization (MASS-PRC) technique. The MASS-PRC process involves continuously mixing and supplying a metal-ligand solution towards the drying front during the solution shearing process to generate an amorphous film, followed by rapid oriented crystal growth through immersion in an amine solution. This method can uniformly produce large-area Ni₃(HITP)₂ films with controllable thicknesses down to several tens of nanometers, high transparency of up to 88.8%, electrical conductivity up to 37.1 S/cm, and a specific surface area of 308.3 m²/g (Fig. 3B). While it enables the production of high-quality, flexible, highly transparent, and conductive Ni₃(HITP)₂ films on a large scale, its relatively smaller specific surface area can be further improved to increase its redox-active sites.

2.3. Fe-based CMOFs

The mixed-valence state of Fe³⁺/Fe²⁺ is the primary reason for the unique electrical properties of Fe-based CMOFs, as the formation of mixed valence states promotes charge delocalization and increases charge density, thereby enhancing the conductivity of MOFs. The design of CMOFs can optimize their electrical conductivity from a physical perspective, where the transport of carriers includes band transport and hopping transport mechanisms. In band transport, charge mobility is determined by the frequency of charge scattering events and the effective mass of the carriers. For conjugated systems composed of energy-matched metal ions and ligands, band transport mechanisms occur, causing the electron orbitals of bonding atoms to overlap and split into continuous energy levels forming bands. Carriers transmit in the delocalized energy band in the form of approximate plane waves, primarily influenced by phonon scattering due to lattice vibrations. In contrast, in the hopping transport mechanism, carriers are localized and reside at specific sites. When the spatial distance and energy difference are small, carriers can hop between adjacent sites, requiring van der Waals forces between molecules and an electron mean free path shorter than the intermolecular distance. Thus, electrons must overcome energy barriers to achieve hopping transport [26]. Benmansour et al. [43] prepared two styrene-based Fe(Ⅱ)/Fe(Ⅲ) mixed-valence 2D CMOFs, [(H₃O)(H₂O)(phenazine)₃][Fe^ⅡFe^Ⅲ(C₆O₄X₂)₃]·12H₂O, both exhibiting a honeycomb layered structure with ferromagnetic order and conductivity (room temperature conductivity of 0.03 and 0.003 S/cm, respectively). Both types of CMOFs are prepared using the interface-assisted synthesis method. This method involves the slow diffusion of a degassed Fe(Ⅱ) solution and a degassed Fe(Ⅲ) precursor [Fe(C₆O₄X₂)₃]³⁻ (X = Cl and Br) solution. This preparation process ensures the simultaneous presence of both oxidation states of Fe in the final compound. Changing X from Cl to Br results in a decrease in room temperature conductivity, which is attributed to the lower electronegativity of Br. The mixed-valence nature of [Fe^ⅡFe^Ⅲ(C₆O₄X₂)₃]⁻ anions promotes electron delocalization, imparting good conductivity to MOFs. The synergistic effect of magnetic ordering in MOFs, combined with their good conductivity, allows for modulation of the conductivity of 2D CMOFs by altering the X ligands in the ligand framework (Fig. 4). Currently, there is relatively limited research on the synthesis of Fe-based CMOFs, thus further exploration of their synthesis methods is warranted.

2.4. CMOFs composites

For some of the aforementioned CMOFs or other MOFs, when a second component is introduced or embedded within their framework, it becomes challenging to classify them precisely as pure MOFs. If there is a distinct separable phase between the MOFs crystals or between the framework and the second component within the MOFs pores, then CMOFs composites are a more appropriate definition. CMOFs composites are composites consisting of MOFs and materials with significantly different properties. Compared to CMOFs, CMOFs composites feature a second component with a clearly defined and separable phase. However, the MOFs phase within the composite retains the attractive characteristics of MOFs, including ultra-high surface area, regular porosity, and intraframework functionality, meaning all the functionalities of the original MOFs are preserved in the CMOFs composites. Various materials, including carbon materials, noble metal nanoparticles, etc., have been used as the second component in designing a range of CMOFs composites, and their application in various fields has been extensively reported. When conductive materials with a continuous phase are used as the second component, the resulting CMOFs composites may exhibit overall conductivity and significantly enhance the composite's catalytic activity [44,45].

2.4.1. Carbon materials

Due to the advantages of carbon materials, such as low cost, high electrical conductivity, high stability, and chemical inertness, various types of carbon materials (e.g., graphene, carbon nanotubes, and carbon nanofibers) have been extensively utilized in the preparation of CMOFs@carbon material composites and applied in efficient electrochemical sensors. These composites integrate the benefits of CMOFs and carbon materials, further enhancing the performance of sensors and providing new insights and methodologies for the development of the electrochemical sensing field.

In the preparation of CMOFs@graphene composites, besides using graphene, various modified forms of graphene, such as graphene quantum dots (GQDs), and reduced graphene oxide (rGO), have also been applied. GQDs consist of single or few-layer graphene nanosheets, featuring a size-dependent photoluminescent bandgap. Some studies have reported the incorporation of GQDs into MOFs, but previous approaches have predominantly used an encapsulation method, i.e., growing MOFs in a suspension of GQDs. This method typically results in the random distribution of GQDs within the MOF crystals. Therefore, Chen et al. [46] successfully incorporated GQDs with an average size of 3.1 nm into the mesoporous porphyrinic Zr-MOF (PCN-222) using a direct impregnation method, forming the GQD-PCN-222 composite. Direct impregnation of GQDs into the MOF enables a continuous and regular arrangement of GQDs within the framework structure. Experimental evidence demonstrates that GQDs are situated within the mesoporous channels of the PCN-222 framework rather than adsorbed on the external surface of PCN-222. The crystallinity and morphology of PCN-222 are preserved, and the composite retains approximately half of the original MOF's porosity with a specific surface area of 1010 m²/g. The conductivity of the MOF increased from 6 × 10⁻¹³ S/cm to 9 × 10⁻¹¹ S/cm. Furthermore, the composite also exhibits excellent electrocatalytic performance (Fig. 5A). While the direct impregnation method achieves a continuous and regular arrangement of GQDs within the MOF framework, this approach necessitates MOFs with larger pore sizes to allow GQDs to enter the MOF channels. However, most MOFs have smaller pore sizes, and there is a lack of interaction between GQDs and MOFs, making the immobilization of GQDs within the MOF framework particularly challenging. rGO is one of the thinnest materials in the world and is an ideal choice for fabricating sensing materials due to its rich edge defects and excellent chemical activity. Hemin can act as a ligand to construct three-dimensional Hemin-MOF through its two carboxyl groups, significantly enhancing enzyme activity and reducing oxidative self-degradation while providing a large surface area to contact target molecules. However, Hemin-MOF has poor conductivity, limiting its application in electrochemical sensors. Wang et al. [47] prepared Cu-hemin MOFs/chitosan-reduced graphene oxide (CS-rGO) composites using a hydrothermal/solvothermal method, which significantly enhanced conductivity and improved catalytic activity through the three-dimensional porous structure of Cu-hemin MOFs. Metal catecholates (M-CAT), composed of HHTP ligands and central metal ions, exhibit high electrical conductivity and charge storage capacity due to π-π conjugation effects. Chen et al. [48] synthesized the best-performing Cu-CAT system using HHTP as a ligand and prepared Cu-CAT@rGO composites through a hydrothermal/solvothermal method. The introduction of rGO reduced the aggregation of Cu-CAT particles, enhancing conductivity and the number of active sites. Growing MOFs on conductive substrates (such as carbon fibers, carbon nanotubes, MXene) can improve electrical conductivity and structural stability. Dong et al. [49] designed flexible composite microelectrodes by growing Ni-MOF nanosheet arrays on rGO/CF using a hydrothermal/solvothermal method. These microelectrodes had a specific surface area of approximately 40 m²/g, and the conductive rGO/CF substrate accelerated electron transfer, enhancing catalytic activity. However, most MOFs cannot grow uniformly on conductive substrates. Manoj et al. [50] formed Cu-MOF/HNTs/rGO composites on HNTs/rGO via a hydrothermal/solvothermal method. The negatively charged groups on the halloysite nanotubes (HNTs) surface attract Cu²⁺ ions, promoting uniform in-situ growth of MOFs without any particle aggregation, and the presence of rGO improves conductivity. In humid environments, CMOFs@rGO composites may face issues with structural and functional integrity. Coating with silica is considered one of the methods to improve water stability. Bhardwaj et al. [51] synthesized a composite of SiO₂-coated Cu-MOF, rGO, and aniline. Under the condition of ammonium persulfate, the polymerization of aniline formed graphene polyaniline (PAni) bridging Cu-MOF and rGO, increasing conductivity and preventing rGO agglomeration. The composite exhibited high porosity and excellent conductivity, with a surface area of approximately 756 m²/g. To avoid rGO damaging the graphene structure and reducing its electrical performance, Hassan et al. [52] used unmodified graphene (G) to prepare highly conductive MOF@graphene composites. The synthesis process allowed for controlled loading of G and porosity adjustment, with the composite's surface area (1156−1078 m²/g) and conductivity (7.6 × 10⁻⁶−6.4 × 10⁻¹ S/m) being proportional to the G content.

Carbon nanotubes (CNTs), including single-walled carbon nanotubes (SWCNTs) and multi-walled carbon nanotubes (MWCNTs), are known for their large surface area, excellent stability, and conductivity. Their integration with MOFs or CMOFs can significantly enhance the conductivity of these frameworks. In CMOFs with non-covalent interactions (such as π-π stacking) between layers, there exists a through-space transfer mechanism from a chemical perspective. In this mechanism, carriers transfer through the overlap of space and orbitals, and increasing orbital overlap can enhance charge mobility. This process can be effectively regulated by adjusting the π-π stacking of ligands [26]. White et al. [53] integrated 2D CMOF (Cu₃(HHTP)₂) with SWCNTs to fabricate a field-effect transistor (FET) sensor based on the SWCNTs@Cu₃(HHTP)₂ composite, whose sensing mechanism is related to the pore-filling of Cu₃(HHTP)₂. The surface area of Cu₃(HHTP)₂ is 280 m²/g, while SWCNTs@Cu₃(HHTP)₂ features a larger surface area (420 m²/g), the variation of which depends on the inherent surface of SWCNTs available for π-π stacking and the presence of carboxyl groups on its surface. Carboxyl groups on the surface of SWCNTs can introduce functional groups that interact with the chemicals connecting the CMOF, determining the interface between materials. The mass loading of SWCNTs and their relative oxidation increase the redox active sites of SWCNTs@Cu₃(HHTP)₂ and regulate its electrical conductivity properties (Fig. 5B). Wang et al. [54] synthesized a Mn-BDC@MWCNTs composite by incorporating MWCNTs into a manganese-based metal-organic framework (Mn-BDC) via a one-step hydrothermal/solvothermal method. Introducing MWCNTs facilitates the cleavage of bulk Mn-BDC into thin layers, which is significant for the electronic conductivity and electrocatalytic capability of Mn-BDC. The Mn-BDC@MWCNTs composite possesses a large surface area (112.72 m²/g) and an average pore radius (17.035 nm).

The synergistic interaction between the structure and conductivity of CMOFs@carbon material composites can significantly enhance their electrocatalytic activity towards various analytes. However, the issue of uneven dispersion of carbon materials within MOFs or CMOFs still exists, potentially affecting the reproducibility of CMOFs@carbon material composites.

2.4.2. CMOFs@precious metal nanoparticles

CMOFs exhibit high porosity and pore structures, thus allowing functional metallic nanoparticles (MNPs) to be anchored or encapsulated within their channels, forming CMOFs@MNPs composites. These possess inherent spatial constraints, effectively preventing the aggregation and growth of small MNPs while providing more catalytic active sites and favorable microenvironments. Therefore, compared to CMOFs@carbon material composites, MNPs within CMOFs@MNPs composites can be well dispersed in small-sized CMOFs. Moreover, functional MNPs, especially precious MNPs, can significantly enhance the catalytic capabilities of CMOFs, showing excellent synergistic effects among components. Based on these characteristics, CMOFs@MNPs composites possess outstanding catalytic and sensing performances.

One method to prepare CMOFs@MNPs composites involves synthesizing CMOFs before the formation of MNPs, using CMOFs as a host material to provide a confined space for MNPs. In this approach, metal precursors are introduced based on different techniques, followed by various reduction methods (e.g., H₂, NH₃BH₃, NaBH₄ and N₂H₄) to incorporate MNPs into the pores of CMOFs, preventing aggregation and restricting their growth. Kim's team [55] first utilized a hydrothermal method with copper acetate and HHTP as raw materials to prepare conductive Cu₃(HHTP)₂, which has a plethora of pores with an average diameter of 2 nm. Subsequently, based on Cu₃(HHTP)₂, Pd or Pt NPs were incorporated, creating Cu₃(HHTP)₂@M (M = Pd or Pt), where the porous structure of Cu₃(HHTP)₂ effectively constrained the growth of Pd and Pt NPs, resulting in ultra-small (~2 nm) and well-dispersed NPs within its pores. The incorporation of Pd or Pt NPs in Cu₃(HHTP)₂ exhibited significantly improved NO₂ sensing performance at room temperature, attributed to the high reactivity of catalytic MNPs and the high porosity of Cu₃(HHTP)₂, though its sensing performance still lags behind other traditional sensing materials. Therefore, Kim's team [56] synthesized PtRu@CMOF incorporating bimetallic nanoparticles (BNPs), where the confinement of BNPs within the pores of Cu₃(HHTP)₂ led to high catalytic activity and stability of PtRu@CMOF. Metal precursors, ruthenium chloride (RuCl₃) and potassium tetra chloroplatinate (K₂PtCl₄), were reduced by sodium borohydride (NaBH₄), generating ultra-small (< 2 nm) PtRu NPs incorporated into the pores of Cu₃(HHTP)₂. Due to the synergistic effect of ultra-small PtRu NPs within a highly porous and conductive matrix, sensors based on PtRu@CMOF exhibited better NO₂ sensing performance compared to those based on Cu₃(HHTP)₂@M (M = Pd or Pt) (Fig. 6A). The preparation of CMOFs@MNPs composites can also be facilitated by introducing MNPs and polymers (such as PVP, MUA, MAA, and PDA) into MOFs' raw materials to promote the growth or assembly of MOFs around MNPs. Gordillo et al. [57] induced the reduction of Au³⁺ ions into gold nanoparticles (AuNP) using polydopamine (PDA), transforming the highly porous but inherently insulating NU-1000 MOF into conductive NU-1000/AuNP and NU-1000/PDA/AuNP composites. Polydopamine synthesis can facilely occur within MOFs' pores through the aerobic oxidation polymerization of dopamine monomers. PDA contains numerous strong reducing groups, such as catechol and amine, capable of reducing Ag⁺, Hg²⁺, and Pd²⁺ metal ions to their respective MNPs. NU-1000/AuNP and NU-1000/PDA/AuNP composites not only achieved significant room-temperature conductivity (~10⁻⁷ S/cm) but also retained considerable porosity and surface area (1527 and 715 m²/g, respectively). The enhanced conductivity of NU-1000/AuNP and NU-1000/PDA/AuNP composites can be attributed to more efficient electron transfer or the introduction of well-dispersed AuNP tunneling within MOFs' pores, a feature lacking in the original NU-1000 (Fig. 6B). Besides the aforementioned methods, in situ growth of zero-dimensional Au-NPs on CMOFs can also prepare composites with excellent catalytic activity. Huang et al. [58] fabricated ultrathin 2D CMOF nanosheets (Cu-HHTP NSs) modified with high-density ultrafine zero-dimensional Au-NPs using a surfactant-assisted solution method. Cu-HHTP, with its large surface area and abundant active metal sites (Cu-O₄), enhances the catalytic activity of Cu-HHTP NSs. Moreover, the extensive exposure of oxygen atoms serves as anchoring points for the deposition of high-density ultrafine Au-NPs (~3 nm) without aggregation. The well-dispersed nature of Au-NPs significantly improved the catalytic activity of Cu-HHTP NSs.

To date, the preparation of CMOFs@MNPs composites still presents numerous challenges, including the precise control over the composites' size and morphology while achieving an appropriate load of MNPs within MOFs or CMOFs. Additionally, the scarcity and high cost of precious MNPs are very real considerations.

2.4.3. Multi-composites

CMOFs@multi-composites are formed by combining two or more different materials (carbon materials, noble metal nanoparticles, etc.) with MOFs and CMOFs. As mentioned before, the introduction of carbon materials or noble metal nanoparticles can effectively improve the conductivity of MOFs and CMOFs, and sensors with excellent conductivity can also be prepared based on CMOFs@MNPs@carbon material composites. Wang et al. [59] functionalized PtPd@Ni-Co hollow nanoboxes (PtPd@Ni-Co HNBs) based on PtPd@Ni-Co hollow nanoboxes (PtPd@NiCo HNBs) and poly(diallyldimethylammonium chloride) graphene (PDDA-Gr) complex developed a hierarchical porous complex Zr-MOF. PtPd@Ni-Co HNBs could provide binding sites for the ligands, and the introduction of PtPd bimetallic nanoparticles improved the conductivity and catalytic activity of the complex. Functionalized PDDA-Gr as a substrate material also improves the conductivity while increasing the electrode surface area for loading more PtPd@Ni-Co HNBs. For highly crystalline CMOFs, band theory is an effective method for understanding their electronic structure, with the Fermi level (E_F) and activation energy (E_a) being key parameters. E_a reflects the energy barrier that carriers need to overcome during excitation. In metallic conductors, there is no band gap due to the overlap of the valence and conduction bands, placing E_F within the overlapping bands filled with free electrons, resulting in high charge density and high conductivity. However, in semiconductors and insulators, E_F is located between the valence and conduction bands. E_a is inversely related to charge density because electrons can be excited from the valence band to the conduction band, leaving holes that create free carriers. There is a certain correlation between Gibbs free energy and E_a, the higher the E_a the greater the change in free energy, which hinders electron transport [24,25,60]. Wang et al. [61] demonstrated a strategy to modulate electrochemical processes on CMOF-based electrodes by different conjugated molecular lines, modifying CMOFs on carbon nanofiber electrodes deposited with gold nanoparticles to prepare Au/RP1/Ni₃HHTP₂. Two conjugated molecular lines with different molecular lengths (4-(thiophene-3-ylethynyl)benzaldehyde (RP1) and 4-((4-(thiol-3-ylethynylalkyl)phenyl)ethynyl)benzaldehyde (RP2)), as well as a heptadecyl-1-thiol (FP) molecule without a conjugated structure were designed to modulate the CMOF. reasonable molecular length and conjugated structure endowed RP1 with effective tunnelling ability, which lowers the Gibbs free energy of the oxidation reaction, and in turn facilitates the non-homogeneous electron transfer from the CMOF layer to the electrode surface. The modification of CMOF nanomaterial Ni₃HHTP₂ on the electrode surface as an electroactive layer provides abundant active sites for electrochemical catalysis. In addition, the porous nanostructure, large surface area and negative charge make Ni₃HHTP₂ a good substrate to enhance the reaction efficiency of positively charged neurochemicals, thus improving the current response. Liu et al. [62] prepared Ni-CAT assembled from highly conjugated tricatecholate, HHTP, and Ni²⁺ by a one-step hydrothermal/solvent-thermal method, and then prepared Ni-CAT in a Ni-CAT/carbon black (CB) complex-modified polarized pencil graphite electrode (PPGE) surface electrodeposited with AuNPs, and synthesized AuNPs/Ni-CAT/CB/PPGE.CB, as a cheap and readily available carbon material, can be embedded in the interstitial space of the unevenly aligned rods of Ni-CAT, which can help to improve the conductivity and stability of the electrode.

2.4.4. Other

The composites obtained by complexing other conductive additives with CMOFs also exhibited good electrical conductivity. The complexation of CMOFs with iodine provides an effective way to improve electrical conductivity. By understanding and designing the E_F and E_a, the electrical conductivity of CMOFs can be further optimized. E_a represents the energy difference between E_F and the valence band maximum (E_VBM) or the conduction band minimum (E_CBM):

$ E_{\mathrm{a}}=E_{\mathrm{F}}-E_{\mathrm{VBM}} $

(3)

or

$ E_{\mathrm{a}}=E_{\mathrm{CBM}}-E_{\mathrm{F}} $

(4)

In undoped semiconductors, E_a corresponds to half of the band gap. Clearly, at a given temperature, a narrow band gap is preferable to a wide band gap because a smaller E_a is associated with a higher charge density. In doped semiconductors, E_F shifts closer to the band edge of the valence or conduction band with the doping level, creating p-type or n-type semiconductors with smaller E_a [25,28]. As shown in Fig. 6C, Sun et al. [63] successfully prepared 2D Cu-HHTP films assembled with Cu²⁺ ions and HHTP ligands on a flexible fabric substrate, and then introduced iodine molecules into the pores of the Cu-HHTP films by the hydrothermal/solvent-thermal method to improve the conductivity of the Cu-HHTP films. The increase in conductivity was mainly due to the redox reaction between the guest molecules and the host system, i.e., the introduction of iodine molecules not only oxidised part of the ligand, but also reduced part of the Cu²⁺ ions to Cu⁺ ions, which facilitated the electron transfer between the guest molecules and the host system, and thus effectively increased the conductivity of Cu-HHTP. The amount of conductivity enhancement was related to the doping time of iodine molecules, and the conductivity of the flexible I₂@Cu-HHTP film was the largest after 48 h of doping with iodine molecules, which was about 0.72 S/cm, more than 30 times that of the pristine MOFs. Considering the challenges in direct MOF thin-film growth, efforts to broaden the MOF library for sensing applications have led researchers to employ polymer/MOF hybrid materials. However, this approach often necessitates a compromise between processability and inherent properties. To address this, Roh et al. [64] proposed a novel hybridization strategy utilizing CMOF and conductive polymer (CP) as complementary ion-electron conductors. This study selected ProDOT-BTD CP, which exhibits reversible redox activity and low onset oxidation voltage and hybridized it with 2D CMOF to form hybrid films. The results demonstrate significant improvements in sensor recovery kinetics, cycling stability, and dynamic range with this hybrid material. The incorporation of CMOF components post-hybridization resulted in hole enrichment, enhancing sensor selectivity and recovery rates while maintaining long-term responsiveness.

3. Electrochemical sensing applications

Electrochemical analysis is an instrumental method based on the electrochemical properties of substances in solution, utilizing electrochemical principles and techniques for qualitative and quantitative analysis of samples. This method primarily relies on the relationship between electrical quantities such as potential, conductivity, and current with the properties of the analytes, offering advantages such as ease of operation, automation potential, fast analysis speed, good selectivity, and high sensitivity. Electrochemical sensors achieve quantitative or semi-quantitative assessment of target analytes by converting specific interactions on the electrode surface (such as antibody/antigen binding or enzyme/substrate reactions) into detectable electrochemical signals (including resistance, capacitance, and current). CMOFs play a crucial role in electrochemical sensors, and their excellent structure and conductivity make them highly applicable for detecting ions, organic pollutants, gases, and biomolecules. Electrochemical sensors based on CMOFs primarily use techniques such as voltammetry, chronoamperometry, electrochemical impedance spectroscopy, and conductometry. Voltammetry includes various methods such as linear sweep voltammetry (LSV), cyclic voltammetry (CV), differential pulse voltammetry (DPV), and square wave voltammetry (SWV), providing diverse options and applications for electrochemical analysis. Breakthroughs in the synthesis techniques of CMOFs have further expanded their application range in the field of electrochemical sensors, enhancing sensor performance [65,66]. The following is the classification of electrochemical sensors based on CMOFs for different detection substances (Table 1).

3.1. Ions detection

Electrochemical sensors based on CMOFs have been widely applied in ion detection due to their high sensitivity, excellent stability, and selectivity. They are capable of detecting not only heavy metal ions such as cadmium ions (Cd²⁺) and lead ions (Pb²⁺) but also anions like nitrite (NO₂⁻). Electrochemical sensors convert the interaction between the sensing element and the target analyte into a measurable signal that is proportional to the concentration of the analyte. Currently, a variety of electroanalytical methods have been employed in electrochemical ion sensors, with the choice of method depending on the characteristics of the interface interactions between the ions and nanomaterials.

3.1.1. Heavy metal ions detection

Cd²⁺ and Pb²⁺ are two typical environmental metal pollutants that pose serious health risks; Cd²⁺ is toxic to organs such as the kidneys and liver, while Pb²⁺ causes problems such as muscle paralysis, anaemia, mental retardation and memory loss. In addition, Pb²⁺ makes people slow to react by reducing synapses, and excessive levels in the body can also cause damage to the kidneys and liver. It is therefore important to establish a method that can detect Cd²⁺ and Pb²⁺. Electrochemical sensors based on CMOFs typically employ SWV for the detection and analysis of heavy metal ions, as SWV offers high sensitivity and precision. The working principle involves applying a square wave potential to the working electrode under electrochemical potential, with a brief linear scan at the start and end of each cycle, forming a pulse. The current response generated by the electrochemical reactions of the chemical substances at the working electrode surface is recorded and analyzed in the SWV curve. Qi et al. [67] prepared a CP-rGO-CoZn·MOF sensing electrode based on conductive carbon paper (CP), reduced graphene oxide (rGO) and CoZn·MOF to establish an electrochemical sensor that can simultaneously detect Cd²⁺ and Pb²⁺ in food samples. On the one hand, the coating of rGO on CP can improve the conductivity of the electrode, and on the other hand, the conductivity of the electrode can be further improved due to the synergistic effect between the two metal elements of the bimetallic CoZn·MOF, which significantly enhances the electrical conductivity of the electrode. In addition, the CP-rGO-CoZn·MOF has a porous network structure, which is conducive to full contact between the target and the electrode, and significantly improves the transmission efficiency. The detection process of both Cd²⁺ and Pb²⁺ was carried out in an acetic acid/sodium acetate solution (pH 4.5) containing 100 mg/L Bi³⁺, and since Bi³⁺ can be deposited on the surface of the sensing electrodes together with Cd²⁺ and Pb²⁺ and exhibit specific redox peaks respectively. Thus, an electrochemical sensor capable of detecting both Cd²⁺ and Pb²⁺ was established. SWV demonstrates that when using the CP-rGO-CoZn·MOF sensing electrode to simultaneously detect Cd²⁺ and Pb²⁺, two distinct peaks appear. When detecting them individually, the peak separation is shorter compared to simultaneous detection. This is possibly due to slight changes in the physical properties during the Cd²⁺/Pb²⁺ and Bi³⁺ reaction processes, resulting in closer peak currents. However, this change is consistent and does not affect their simultaneous detection. The peak currents of the sensing electrode gradually increased with the increase of Cd²⁺ and Pb²⁺ concentrations and were linear in the concentration range of 1 nmol/L-35 µmol/L, with the limits of detection (LODs) as low as 0.565 nmol/L (Cd²⁺) and 0.588 nmol/L (Pb²⁺). The recoveries of Cd²⁺ and Pb²⁺ in food samples were in the range of 97.5%-105.9% and 94.3%-109.6%, respectively, indicating that the established electrochemical sensors responded well to the targets, and their relative standard deviations (RSDs) were not more than 5.817%, demonstrating their potential for practical applications (Fig. 7).

3.1.2. Nitrite detection

In addition to exhibiting exceptional performance in the detection of heavy metal ions, electrochemical sensors based on CMOFs also show outstanding capabilities in the detection of anions, especially in the electrocatalysis and redox abilities for NO₂⁻. NO₂⁻ is a common environmental pollutant and is widely used as a preservative in the food industry. The World Health Organization has established a maximum limit for NO₂⁻ in drinking water at 65.2 µmol/L (3 mg/L), highlighting the importance of controlling the intake of NO₂⁻. Due to its strong oxidizing properties, inadvertent consumption of NO₂⁻ can oxidize the low-valence hemoglobin in the human body into high-valence methemoglobin, causing the hemoglobin to lose its oxygen-carrying function, leading to hypoxia and potential poisoning. Moreover, NO₂⁻ is carcinogenic; it interacts with amines in food to form potent carcinogenic nitrosamine composites, increasing the risk of cancer in the esophagus, stomach, and intestines over long-term consumption. Therefore, there is a need to develop a detection strategy for NO₂⁻ that is highly sensitive, selective, and quick to respond. Currently, electrochemical sensors based on CMOFs for NO₂⁻ detection primarily employ CV for analysis. CV involves scanning the potential at a linear rate on the working electrode while simultaneously measuring and recording the current, resulting in a potential-current curve. During the potential scan, electroactive substances on the electrode surface undergo oxidation or reduction reactions, producing characteristic peaks. During the reverse scan, reverse peaks may appear, providing information on reaction kinetics and mechanisms. This method is simple to operate, sensitive to reaction kinetics, and capable of simultaneously obtaining information on both oxidation and reduction processes. Chen et al. [46] synthesized GQD-PCN-222 composites which exhibited excellent redox capacity for NO₂⁻. The electrochemical detection of NO₂⁻ was carried out using GQD-PCN-222 thin films deposited on FTO conductive substrates, and the CV curves showed that the current signals increased linearly with NO₂⁻ concentration in the linear range of 40–18,000 µmol/L, with a LOD of 6.4 µmol/L. Lu et al. [68] synthesized a two-dimensional nickel phthalocyanine-based MOF (NiPc-MOF) via a hydrothermal/solvothermal method and employed it to construct a non-enzymatic electrochemical sensor for detecting NO₂⁻. Owing to its excellent conductivity and large surface area, all the NO₂⁻ was adsorbed on the surface of the 2D NiPc-MOF electrode, and the 2D NiPc-MOF exhibited excellent electrocatalytic activity for NO₂⁻ with an ultra-wide linear range of 0.01–11,500 mmol/L and a low LOD of 2.3 µmol/L.

Summarizing the above, electrochemical sensing platforms show ideal application prospects in the detection of heavy metal ions and nitrites. However, the current range of ions that can be detected by CMOF-based electrochemical sensors is somewhat limited. Beyond detecting Cd²⁺, Pb²⁺, and NO₂⁻, the development of CMOF-based electrochemical sensors for other ions (such as Cu²⁺ and Hg²⁺) is still in progress. While copper is an essential trace element for many biological processes, elevated levels of Cu²⁺ may lead to cancer and other genetic diseases. Mercury, on the other hand, can damage the endocrine, nervous, and immune systems, and long-term consumption of water containing trace amounts of mercury can even cause cumulative poisoning. Therefore, by tailoring the synthesis of CMOFs to endow them with specific recognition capabilities, it is possible to effectively detect a wider variety of ions, thereby broadening the application range of CMOF-based electrochemical sensors. This holds significant real-world importance and potential value, playing an indispensable role in expanding their applications across various fields.

3.2. Organic pollutants detection

Organic pollutants are organic composites that pollute the environment and can be divided into natural organic pollutants and synthetic organic pollutants according to their sources. Natural organic pollutants mainly refer to the natural chemical reaction or metabolism of living organisms, which produces a variety of organic composites that are harmful to human health and pollute the environment, such as aflatoxin, ethyl carbamate. Synthetic organic pollutants, on the other hand, refer to all kinds of organic composites produced by modern industry, such as dyes, detergents, pesticides, plastics. Detecting organic pollutants can prevent them from affecting the ecological balance and causing health problems. By detecting indicators of organic pollution in advance using CMOF-based electrochemical sensors, pollution can be effectively prevented, and problems avoided before they occur.

3.2.1. Antibiotics detection

Chloramphenicol (CAP) is an antibiotic that has been widely used in aquaculture. However, the misuse of chloramphenicol inevitably results in residues in animals and eventually in humans through the food chain, causing a number of serious side effects including bone marrow suppression, leukaemia and fatal irreversible aplastic anaemia. Therefore, the establishment of a rapid and sensitive technique for the detection of CAP residues in food has attracted much attention in today's society. As shown in Fig. 8, Wang et al. [59] constructed a Zr-MOF-labelled electrochemical aptasensor using PDDA-Gr/PtPd@Ni-Co HNBs as electrode modification materials. PtPd@Ni-Co HNBs have excellent conductivity and provide binding sites for aptamers, and functionalized PDDA-Gr as substrate material improves its dispersion and conductivity, which can be successfully used to increase the electrode surface area and support more PtPd@Ni-Co HNBs, facilitating signal amplification. In the presence of CAP, Cycle I is triggered externally, releasing a large amount of trigger DNA, after which the trigger DNA and Exo Ⅲ initiate Cycle Ⅱ, resulting in the exposure of the captured DNA, allowing the signaling probe (MB/HP-UiO-66/signaling DNA) to attach to the electrode and generate a signal. The rational design and amplification strategy employed resulted in a sensor with higher sensitivity and better selectivity for CAP detection. In addition, graded porous Zr-MOFs (HP-UiO-66) were used as signaling probes and showed a higher loading capacity for signaling molecules than conventional UiO-66. With these advantages, the sensor has a linear range of 10 fmol/L−10 nmol/L and a LOD of 0.985 fmol/L.

3.2.2. Pesticide residue detection

Due to the widespread use of imidacloprid (IMI), its residues in agricultural products have become common pesticide contaminants. Therefore, there is a need for accurate quantitative analysis of IMI in various samples, especially plant products. Various methods have been developed for the determination of IMI, including high performance liquid chromatography (HPLC), liquid chromatography tandem mass spectrometry (LC-MS/MS), gas chromatography tandem mass spectrometry (GC–MS/MS) and immunoassay. However, these analytical methods are costly and time consuming. Therefore, there is a need to develop inexpensive, convenient and sensitive methods for the determination of IMI. electrochemiluminescence (ECL) sensors have received considerable attention from researchers in pesticide residue analysis in recent years due to their low background noise and inherent high sensitivity. Ma et al. [69] successfully prepared mixed-valence ultrafine one-dimensional Ce-MOF nanowires via a micelle-assisted biomimetic pathway and applied them for the detection of IMI in plant foods. The Ce-MOF nanowires have a size of about 50 nm and possess good water stability and high electrical conductivity. In Ce-MOF, Ce(Ⅲ) can catalyze the production of superoxide anions (O₂^•−), thereby enhancing the generation efficiency of O₂^•−. Subsequently, the luminescent amine radicals and a large amount of superoxide anions produce the luminescent group AP^2−•, resulting in an enhanced ECL of the system. The ECL sensor developed using these nanowires in combination with molecular imprinting technique has a linear range of 2–120 nmol/L for the detection of IMI and a LOD of 0.34 nmol/L.

Paraoxon is an organophosphorus compound commonly used as an insecticide, but it is highly toxic and prone to human health hazards. The Cu₃(THQ)₂-based sensor prepared by Niu et al. [30] showed excellent immunity to interference, good stability, fast response time and extremely low LOD for paraoxon (an organophosphorus model compound) (0.37 ng/mL, 27 times below the acceptable limit). During the electrooxidation of Cu₃(THQ)₂ and the addition of analytes, a Cu⁺/Cu²⁺ valence state change cycle occurs. The charge transfer between Cu₃(THQ)₂ and the analyte is essential for the electrocatalytic reaction. The sensor can be used for the determination of paraoxon in water, soil, vegetable and fruit samples and is applicable for the rapid detection of real samples.

3.2.3. Toxin detection

Cadaverine (Cad) is considered to be an important chemical marker of food spoilage and can also be used to monitor food freshness. Presently, the analysis of toxins using electrochemical sensors based on CMOFs predominantly employs chronoamperometry. Chronoamperometry, also known as amperometric timing method, determines the concentration of substances or the rate of electrochemical reactions by recording the relationship between current and time (I-T curve). This method is simple to operate, suitable for real-time monitoring and rapid analysis, and particularly effective for detecting low concentration substances due to its high sensitivity. However, it is essential to consider environmental factors (such as temperature and humidity) that may affect the measurement results to ensure data accuracy and reliability. Zhang et al. [70] prepared an electrochemical sensor based on IC-CuTHPP-MOF for the detection of Cad. During the preparation process, if an excess of Cu(NO₃)₂ is introduced, in addition to serving as metal nodes on the metalloporphyrin compound ring, unreacted Cu²⁺ will also be present. The direct coordination effect between Cad and Cu²⁺ imparts an irreversible response to the sensor, even completely restricting the movement of free Cu²⁺. The strong complexation between Cad and Cu²⁺ results in a decrease in capacitance. Even after heating and vacuum treatment, its normal state cannot be restored. As the mobile ions are depleted, the sensor's current gradually decreases. The sensor also exhibited good long-term stability and fast response time (13.5 s) with an LOD of 4.9 nL for Cad and was able to respond quickly to spoiled meat.

Deoxynivalenol (DON) is one of the most common mycotoxins in cereals and can cause gastrointestinal inflammation even in trace amounts. Wen et al. [71] developed a simple electrochemical aptamer sensor for the rapid and sensitive determination of DON based on multifunctional N-doped Cu-metal-organic skeleton (N-Cu-MOF) nanomaterials. As the number of aptamers on the electrode decreases, the peak current increases due to the increasing number of non-conducting aptamers blocking the electron transfer from the N-Cu-MOF. When DON is detected, the aptamers are removed from the N-Cu-MOF and the signal appears and is proportional to the concentration of DON. The sensor showed high sensitivity and good selectivity with a linear detection range of 0.02–20 ng/mL and a LOD of 0.008 ng/mL.

3.2.4. Plastic additives detection

Bisphenol A (BPA) is an endocrine disruptor that acts like oestrogen and is widely used in the manufacture of plastics. Exposure to trace amounts of BPA can cause brain damage, immune system failure, thyroid dysfunction, etc. At present, electrochemical sensors leveraging CMOFs predominantly utilize DPV techniques for the detection of plastic additives. DPV is a technique that is not affected by residual currents, allowing for rapid and sensitive measurements. This method applies potential pulses at a constant amplitude, incrementing the potential with time, where each successive pulse potential is slightly higher than the preceding one. Chen et al. [48] synthesized a series of electrically conductive metal-organic skeletons (M-CATs) composed of different metal ions, such as conductive Fe-CAT, Co-CAT, Ni-CAT, Cu-CAT and Zn-CAT, which were used for the electrochemical detection of BPA in beverage bottles. The electrodes prepared with conductive Cu-CAT gave the maximum oxidation peak of BPA by DPV technique, a wide linear detection range (0.05−100 µmol/L) and a low LOD (4.9 nmol/L).

3.2.5. Other

The thiol compound N-acetyl-l-cysteine (NAC) acts as an antioxidant to protect cells from cytotoxic toxicity and has many therapeutic applications, so its quantification is important in clinical research. Zhuge et al. [72] fabricated NiPc-Cu MOF-based electrochemical sensors for sensitive NAC detection. NiPc-Cu MOF was used as a photoelectrochemical (PEC) sensor for sensitive NAC detection because NAC can interact with Cu composites, and the photocurrent generated by NiPc-Cu MOF decays after interaction with NAC. The sensor detected NAC in the concentration range of 0.0125–42.5 µmol/L with a LOD of 5.2 nmol/L.

Perfluoroalkyls (PFAS) are accumulating in the environment, drinking water and food and have become a global health threat, making their effective detection and trapping extremely important. Gumyusenge et al. [73] prepared a chemoresistive sensor based on a Cu-HHTP CMOF thin film for the detection of PFAS in drinking water. Due to the excellent electrostatic attraction between the Cu-based MOF and PFAS and the electrochemical interactions, the sensor showed high sensitivity to PFAS at concentrations as low as 0.002 ng/L. Specifically, the electron cloud at each coordination node within the CMOF film can enhance the electrostatic attraction between the CMOF and PFAS. After PFAS adsorbs onto the surface of the CMOF film, this electrostatic attraction and the interaction between the electron-rich CMOF and PFAS alter the overall oxidation state of Cu-HHTP, leading to significant changes in the film's conductivity. This change in conductivity is the key mechanism for the sensor's high sensitivity detection.

Electrochemical sensors based on CMOFs have the advantages of high sensitivity, good selectivity and ease of operation in the detection of organic pollutants. Although significant progress has been made, further research is needed to move these sensors from laboratory studies to practical applications. For example, considering the importance of factors such as mass production, field applications, low-cost manufacturing and environmental protection in practical applications, we need to optimize and improve these sensors more comprehensively.

3.3. Gases detection

Electrochemical sensors can be used for gas detection to prevent people from breathing toxic gases that pose a health threat, as well as to prevent the formation of explosive environments. CMOFs-based electrochemical sensors can detect gases such as ammonia (NH₃), carbon dioxide (CO₂), hydrogen sulfide (H₂S), methanethiol (CH₃SH), nitrogen dioxide (NO₂), nitric oxide (NO) and acetone (C₃H₆O). The core of the sensing mechanism is the reaction or adsorption process between gas molecules and the surface of the sensing material, which leads to the transfer of electrons or holes. Therefore, when the sensing layer interacts with the target gas, the resistance of the electrochemical sensor changes accordingly. In addition to this basic sensing mechanism, chemical sensors have many advantages. It is not only low in manufacturing cost, but also easy to integrate with various electronic devices, and easy to miniaturize, which makes it a wide range of applications in the field of gas detection.

3.3.1. Ammonia detection

Ammonia (NH₃) is one of the most hazardous environmental pollutants in industrial processes and can cause damage to the skin, eyes and respiratory tract at high exposures. In the biomedical field, NH₃ is also one of the metabolites of the human body, and the excess of NH₃ in human exhaled breath may be related to several diseases associated with liver and kidney dysfunction. Therefore, the development of high performance NH₃ sensors is of great importance in the biomedical and environmental fields. Yao et al. [74] synthesized a CMOF (Cu₃(HHTP)(THQ)) nanowire with a π-conjugated structure, high conductivity (σ ≈ 2.53 × 10⁻⁵ S/cm) and high porosity (about 441.2 m²/g). The semiconducting nature of Cu₃(HHTP)(THQ) has gas-sensitive properties at room temperature due to its semiconducting nature and low activation energy. As a result, chemoresistive gas sensors based on Cu₃(HHTP)(THQ) have been prepared for the detection of NH₃ with LOD as low as 0.02 ppm. Compared to single-ligand-based CMOF, the conductivity baseline of the sensing material is significantly reduced by approximately two orders of magnitude, which substantially enhances the material's sensitivity to minor charge transfers during low-concentration gas adsorption. This phenomenon may be attributed to the complexes formed between NH₃ and Cu⁺ and Cu²⁺, as reflected by the specific absorption peaks observed in infrared spectra and the resulting red shift in the C–O vibration mode (v(C–O)), indicating high selectivity towards NH₃. This selectivity is likely due to the strong interaction between the gas molecules and the CMOF framework, leading to lattice expansion of the CMOF upon NH₃ adsorption. This lattice expansion serves as direct evidence of strong interactions, in contrast to the lack of similar expansion in the presence of O₂. This suggests a weaker interaction between O₂ and the CMOF framework, thus validating the principle of high sensitivity and selectivity of the studied sensing material towards NH₃. Sanjeev et al. [51] have synthesized SiO₂CuOF-graphene-PAni composites for the detection of NH₃. During the sensing process, the SiO₂CuOF-graphene-PAni composites provide a proton with NH₃ to form NH₄⁺ ions, and then the NH₄⁺ ions are rapidly decomposed to form NH₃ and H⁺, and the available hydrogen ions help to improve the sensor recovery characteristics to its original conductivity level. The sensor can sensitively detect NH₃ over a linear range of 1–100 ppm with a LOD of 0.6 ppm. Michael et al. [75] prepared a reversible chemoresistive sensor by simple drop casting of Cu₃(HITP)₂ with an LOD of 0.5 ppm for NH₃. Although CMOFs can detect NH₃ gas in air, CMOFs synthesized based on solution reaction still suffer from the drawbacks of low sensitivity, lack of stability and poor reproducibility. This is mainly due to the fact that it is still challenging to integrate CMOFs into sensing devices while maintaining activity and conductivity. In order to advance the fabrication process of chemoresistors based on CMOFs, Chen et al. [37] prepared gas sensors for the detection of NH₃ based on 10 nm thick Cu-BHT films at room temperature. The crystalline particles on the surface of the Cu-BHT films can introduce Cu_2c sites, and their response to NH₃ is positively correlated with the density of Cu_2c sites on the film surface. During the sensing process, when NH₃ molecules are adsorbed by Cu_2c sites, electrons from NH₃ are transferred to the film and increase its Fermi energy level. In addition, the electrons bind to holes, reducing the carrier concentration, and the Cu-BHT film shows an increase in resistivity and HOMO level after reacting with NH₃ at a concentration of 1–100 ppm for 2 min (Cu-BHT-2 min) at room temperature. Due to the excellent intrinsic conductivity of Cu-BHT, the response recovery curve of Cu-BHT-2 min showed that the current decreased, i.e. the resistance increased, and the output current of the sensor could reach tens of microamperes when the driving voltage on the electrodes was only 0.01 V. The sensor was also able to achieve a high HOMO level after 2 min at room temperature. The sensor has good selectivity, fast response (58 s), low LOD (0.23 ppm), low driving voltage (0.01 V), good reusability (CV = 0.145%) and long-term stability, as well as low power consumption and long lifetime (Fig. 9A). Electrochemical sensors integrating CMOFs predominantly harness advanced conductometry methodologies for the precise detection of gases. Conductometry is an electrochemical method that utilizes conductivity (or conductance) to analyze chemical substances. The fundamental principle involves determining ion concentration or the progress of a chemical reaction by measuring conductivity, the higher the ion concentration, the greater the conductivity. Conductance (G) is defined as the reciprocal of resistance (R). In kinetic studies, by measuring conductance changes at different time points, one can obtain conductance-time or resistance-time curves (G-T or R-T curves) to investigate reaction rates and mechanisms. Conductometry is simple to operate, highly sensitive, widely applicable, and is a commonly used electrochemical analysis method. Huang et al. [76] reported a hierarchical structure-accelerated interfacial dynamics strategy to improve interfacial gas transfer on hierarchical CMOF membranes. Graded CMOF membranes were synthesized by using π-conjugated ligands (HHTP or 2,3,9,10,16,17,23,24-octahydroxycopper phthalocyanine (PcCu(OH)₈)) in situ transformed insulating MOF (ZIF-8 or ZIF-67) membrane precursors with nanopore shells (~1.2 nm) and hollow internal voids (~500 nm). The introduction of hollow structures into CMOF membranes can increase the gas permeability and thus the speed of movement of gas molecules towards the film surface, which is 8.4 times higher than that of bulk-type films (MOF films without hierarchical porous structure synthesized by hydrothermal method). The CMOF film-based chemoresistive sensor showed a faster response to ammonia at room temperature than other reported ammonia chemoresistive sensors, and the response was 10 times faster than that of the bulk-type film. Among them, the chemoresistive ammonia sensor based on Zn-HHTP-H showed the fastest response at room temperature (response time of 9.1 s) with a LOD of 39.9 ppb. In addition, Yao et al. [35] reported the assembly of 2D conductive Cu₃(HHTP)₂ thin films by spray layer-by-layer liquid phase epitaxy, in which crystalline Cu₃(HHTP)₂ nanofilms were prepared by successively spraying metal nodes and organic ligands in solution with an increase in thickness of 2 nm per cycle. By adjusting the number of sprays, the thickness of Cu₃(HHTP)₂ can be easily controlled in the range of 20–100 nm. The films exhibited high NH₃ sensing performance and low LOD (0.5 ppm) at 20 nm because the films were easily adsorbed by NH₃. Heterostructured metal-organic framework MOF-on-MOF films have the potential to cascade the various properties of different MOF layers in a sequential manner, thereby generating functionality that cannot be achieved with a single MOF layer. Therefore, Yao et al. [77] also reported a van der Waals interaction dependent method to obtain highly oriented MOF-on-MOF thin films by depositing a Cu-TCPP layer on a Cu-HHTP layer. This method is convenient and avoids the lattice matching conditions that have to be considered for the growth of MOF-on-MOF films in previous methods. The Cu-TCPP-on-Cu-HHTP films showed excellent selectivity in NH₃ detection with a LOD of 0.12 ppm. The Cu-HHTP 3D films prepared by Lin et al. [78] not only have good crystallinity, orientation and precisely controllable nanoscale thickness, but can also detect NH₃ at the ppt level. Similar to the Cu-HHTP 2D films, the Cu-HHTP 3D films also have a thickness-dependent sensitivity. This is because relatively thin films have fewer active sites within them, while relatively thick films have longer gas diffusion paths. Therefore, the response of Cu-HHTP 3D films initially increases with increasing film thickness, reaching a maximum at 20 nm and then decreasing. Compared to Cu-HHTP 2D films, Cu-HHTP 3D films have more efficient charge transport, larger active surface area and more exposed active sites. As a result, the sensor based on the 3D film has been optimized for LOD by a factor of 1000 (~87 ppt), with a 250% increase in response to 1 ppm NH₃ and a 130% increase in response speed. The detection of NH₃ can also be used to determine and monitor the freshness of food. Huang et al. [79] prepared gas sensors based on MOF@SnS₂ composites for the detection of the food spoilage gas NH₃. NH₃ tends to be centered on Cu atoms as a central adsorption site, and therefore in the MOF material the charge transfer occurs mainly in the vicinity of the Cu atoms. However, in hybridization, charge transfer also occurs at the interface between the SnS₂ and MOF layers, so more atoms are involved in the sensing process. The greater variation in carrier concentration of the hybrids makes the sensor more sensitive. Compared to the original MOF-based sensor, the sensor has a four times higher response, an extremely low LOD (experimental: 125 ppb; theoretical: 9.84 ppb) and improved selectivity for the putrefactive gas NH₃.

3.3.2. Hydrogen sulfide detection

Hydrogen sulfide (H₂S) is a colorless, highly toxic, acidic gas with a peculiar rotten egg smell. Even low concentrations of H₂S can damage the sense of smell, and high concentrations are rather odorless because high concentrations of H₂S can paralyze the olfactory nerves. A 2D CMOF (Co₃(HITP)₂) was prepared and applied to H₂S sensing at room temperature (RT) by Sun et al. [80]. The Co₃(HITP)₂ sensor showed high sensitivity and good selectivity for H₂S under different relative humidity conditions. Furthermore, the gas sensing performance of the sensor was further improved by embedding different amounts of Pd NPs in Co₃(HITP)₂. The 2 mol% Pd-functionalized Co₃(HITP)₂ sensor showed the best H₂S sensing performance at different humidity levels. By extending the catalytic metal NPs to Au and Pt, the Co₃(HITP)₂ sensors loaded with Au or Pt also exhibited significantly improved H₂S sensing performance with high response and low LOD (0.7, 1.4 ppm (25% RH)). Miao et al. [34] prepared TOM-Cu₃(HITP)₂ thin films, which do not differ significantly in composition from ordinary Cu₃(HITP)₂ MOFs. However, the three-dimensionally ordered submicron macroporous (TOM) morphology resulted in a significant increase in the sensitivity of the TOM-Cu₃(HITP)₂ films to H₂S gas. The TOM-Cu₃(HITP)₂ films achieved an electrical resistance response of 78.5–80 ppm H₂S gas at room temperature, which is 6.7 times higher than that of Cu₃(HITP)₂ without the TOM structure. Lee et al. [42] prepared a sensor for the detection of H₂S based on Ni₃(HITP)₂. Ni₃(HITP)₂ was exposed to H₂S, and the products of Ni-catalyzed oxidation, sulphides and sulphites, were adsorbed. The detection limit of this sensor, calculated from linear fit and resistive noise, was 3 ppb, which can be used for portable gas sensing applications. Cho et al. [81] prepared MOF@MOF nanocomposites (Ni-HHTP@UiO-66-NH₂) by integrating the conductive 2D MOF Ni-HHTP with the chemically stable and highly porous 3D MOF UiO-66-NH₂. The hierarchically assembled 2D-MOF@3D-MOF exhibited novel interfacial properties with synergistically enhanced sensing performance for toxic H₂S gases, as well as low LOD (1.4 ppb), superior sensitivity (ΔR/R₀ = 3.37) and excellent selectivity. Zhang et al. [82] used a combination of in situ etching and layer-by-layer liquid phase growth to fabricate conductive and thickness-controllable CuHHTP-coated Cu₂O (Cu₂O@CuHHTP) for humidity-independent detection of H₂S at room temperature. Compared to below 75% RH, the response to H₂S was reduced by only 2.6%, a 9.6-fold improvement over the bare Cu₂O sensor, which is attributed to the CuHHTP layer hindering the adsorption of water molecules. In addition, a portable alarm system has been developed to monitor food quality by tracking the release of H₂S. They have a high potential for food quality assessment with a relative error within 9.4 per cent compared to gas chromatography.

3.3.3. Nitric oxide and NO₂ detection

Nitrogen dioxide (NO₂) is a toxic gas that is a strong irritant, easily pollutes the environment and is a cause of ozone and acid rain. Lim et al. [83] introduced laser-induced graphene (LIG) as a growth platform for Cu₃HHTP₂ to enable real-time monitoring of ppb-level NO₂. First, the nanostructured MOF grown on LIG was able to mimic the hierarchical macroscopic/microporous structure of the lung, thereby accelerating gas transport. In addition, by increasing the exposed area, the MOF can take full advantage of its open metal sites and edge ligands to adsorb guest molecules. As a result, the LIG@Cu₃HHTP₂-based NO₂ sensor had the shortest response/recovery time (16 s/15 s) and the lowest LOD (0.168 ppb), even at room temperature and under atmospheric conditions (Fig. 9B). PtRu@cMOF-based sensors were prepared by Park et al. [56] Due to the bimetallic synergy of the PtRu NPs and the high surface area and porosity of the CMOF, the sensors exhibited remarkable NO₂ chemoresistive sensing performance. Dynamic resistance changes were detected at 0.2–3 ppm NO₂ concentration, although the response time of the sensor was slow at sub-ppm NO₂ levels, PtRu@cMOF displays 0.2 ppm with ultra-low LOD. Currently, most reported 2D CMOFs are limited to ligands with specific high symmetry conjugated aromatic nuclei. This has resulted in only a few available topologies for 2D CMOFs, such as triangular, tetragonal and hexagonal lattices, due to limitations of both the ligands and the synthesis methods. Su et al. [84] developed a new non-planar salphen ligand with C_2v symmetry (6OH-salphen) and constructed 2D Cu-salphen MOF by in situ one-pot synthesis, which is characterized by the metal ligand-induced planarization of the salphen core. The presence of the N₂O₂ pocket of 6OH-salphen endows the 2D Cu-Salphen-MOF with higher metal density, shorter metal spacing and narrower band gap, thus enabling it to exhibit a high response to NO₂ with a detection range of (1–100 ppm) and a LOD of 0.28 ppm.

Nitric oxide (NO) is widely distributed in the tissues of living organisms, especially in nervous tissue, and is a novel biological messenger molecule. A small amount of NO has vasodilator and memory enhancing functions in the human body, but too high a concentration can lead to methemoglobinemia, which is dangerous to human health. Aykanat et al. [85] synthesized Bi-HHTP assembled from bismuth ions and HHTP ligands and prepared chemoresistive gas sensors based on Bi-HHTP. Two volatile organic composites, NO and NH₃, interact with water molecules through different hydrogen bonding mechanisms and displace them in the pores of the Bi-HHTP, triggering structural changes that facilitate the migration of carriers. The LODs of NO and NH₃ were 0.15 ppm and 0.29 ppm for the detection of NO and NH₃, respectively, at low driving voltage (0.1–1.0 V) and room temperature. Eagleton et al. [38] prepared a Cu₃(HHTP)₂-based chemoresistive sensor for the detection of NO and H₂S with an LOD of 1 ppm. NO interacts with the Cu center of Cu₃(HHTP)₂ and NO is oxidized to NO₃⁻. The electrons consumed in this process can be transferred either by conversion of Cu²⁺ to Cu⁺ or by in-frame oxidation of the HHTP ligands. The oxidation of H₂S and reduction of Cu adds electrons to the valence band of the CMOF, thus reducing the carrier concentration. Xu et al. [86] fabricated a ppb-level chemoresistive sensor for nitrogen oxides (rGO/PDDA/Co₃(HITP)₂) by assembling GO with a conductive π-d conjugated metal-organic framework, Co₃(HITP)₂, in the presence of poly dimethyldiallylammonium chloride (PDDA). The nanocomplex showed significant sensitivity and selectivity for NO in various gas analytes due to its porous structure and numerous active sites. The incorporation of Co₃(HITP)₂ enhanced the adsorption of the nanocomplex for NO, which was attributed to the π-feedback effect of d-electrons in the Co metal center on NO gas. The chemoresistive sensor showed a low LOD of 11.2 and 6.8 ppb for NO and NO₂, respectively, and a response/recovery time of 24/41 s for 200 ppb NO. rGO/PDDA/Co₃(HITP)₂ could achieve a sensitive and fast response to NO_x at room temperature (RT). By adding a certain amount of NO to an exhaled breath (EB) sample collected from a healthy person to simulate the EB of a patient with airway inflammation, the sensor could successfully distinguish the healthy person from the simulated patient, and it had excellent capability in EB detection. Meng et al. [87] fabricated a chemoresistive gas sensor based on nickel phthalocyanine and nickel naphthalocyanine bimetallic CMOF (NiPc- and NiNPc-based 2D CMOF), in which a chemoresistive response was generated by charge transfer triggered by analytes adsorbed on the CMOF. At low driving voltages (0.01–1.0 V), the sensors exhibited excellent sensitivity with LODs of NH₃ (0.31–0.33 ppm), H₂S (19–32 ppb) and NO (1.0–1.1 ppb), respectively. In order to advance the process of manufacturing chemoresistors based on CMOFs, effective ways of integrating CMOFs with sensor devices need to be found. In addition to processing into thin films, the combination of CMOFs with textiles can be considered to provide more possibilities for the fabrication of sensor devices. Merry et al. [88] prepared Ni₃HITP₂ and Ni₃HHTP₂ MOFs based on textiles. The composite textiles have high electrical conductivity, high flexibility and good mechanical stability due to the close fixation of the CMOFs on the fabrics. The charge transfer and interaction occurs between the CMOFs and the gases, and the sensors have theoretical LODs of 0.16 and 1.4 ppm for NO (0.1–80 ppm) and 0.52 and 0.23 ppm for H₂S (1–80 ppm), respectively. 0.16 and 1.4 ppm for NO (0.1–80 ppm) and the theoretical LOD for H₂S (1–80 ppm) is 0.52 and 0.23 ppm, respectively.

3.3.4. Other

CO₂ has great potential as a gas phase tracer in natural, domestic and industrial processes. Cu₃HIB₂ prepared by Ivo et al. [89] shows excellent selectivity and CO₂ sensing properties in the linear range (400–2500 ppm). When Cu₃HIB₂ is exposed to ambient conditions, CO₂ undergoes electron-withdrawing interactions with the amine, corresponding to charge trapping of the material, as the amine is an integral part of the conjugated backbone of the material, leading to the reversible formation of CO₂ adducts or bicarbonates in Cu₃HIB₂. The response of the Cu₃HIB₂-based sensor was linear with respect to the CO₂ level in the range of 10%-80% RH, and the CO₂ sensitivity was almost independent of RH (Fig. 9C).

CH₃SH has a peculiar odor, is toxic, has lacrimating and emetic effects, and is harmful to humans either by direct contact or inhalation of the vapor. Li et al. [90] prepared a sensor based on Cu-TCPP IC-MOF. High selectivity was achieved by ion carrier-analyte interaction, with LODs as low as 1 ppb and 1 ppm for H₂S and CH₃SH, respectively.

C₃H₆O is a toxic substance, direct contact will have an irritating effect on human skin and mucous membranes, anesthetize the nervous system, inhibit respiration, resulting in breathing difficulties, exposure to high concentrations of C₃H₆O on the liver, kidneys, pancreas will also cause damage. In addition, C₃H₆O is often used as a raw material for drugs by unscrupulous elements, and its vapor is heavier than air, which can be diffused to a considerable distance at a lower level, and there is a danger of catching fire when it meets an ignition source, and it can also form explosive mixtures with the air. Du et al. [91] prepared a chemoresistive gas sensor based on Zn-BTC nanosheets for detecting the ppb level of C₃H₆O. Due to the presence of a functional interface, the experimental detection limit of C₃H₆O concentration can be as low as 100 ppb with a dynamic response linearity of 99%. Zhou et al. [92] prepared a gas sensor based on Mn₂[TTF]_x[NiS₄]_1−x (0 ≤ x ≤ 1). Detection was evaluated at different ratios, and Mn₂[TTF]_0.78[NiS₄]_0.22 showed the highest sensitivity to C₃H₆O (20 ppm), which was higher than that of the analogue based on a single linker, highlighting the synergistic effect of the mixed-linker MOFs.

In recent years, CMOFs-based electrochemical sensors have been investigated in the field of gas detection and several research teams have achieved innovative results. However, further improvements in the performance of these sensors are needed to make them widely available for commercial applications. For example, the poor chemical stability of most CMOFs limits their practical use in harsh environments. Therefore, improving the stability of CMOF-based sensors for gas detection is one of the most pressing issues to be addressed today, which is of great importance in promoting their commercial applications.

3.4. Biomolecules detection

CMOFs, characterized by their high porosity, tunable topological structures, and ease of functionalization, are well-suited for the detection of various biomolecules. Additionally, CMOFs exhibit exceptional catalytic activity, often serving as nanozymes in biomolecule detection. Furthermore, by designing metal clusters or organic ligands, CMOFs can act as signal probes or nanocarriers for biomolecule detection. Electrochemical sensing, a powerful analytical tool, possesses the capability for rapid detection of biomarkers. Hence, CMOF-based electrochemical sensors can be employed for biomolecule detection.

3.4.1. Small biomolecules detection

The detection of small biomolecules (such as hydrogen peroxide, glucose, ascorbic acid, and dopamin) through CMOFs-based electrochemical sensors has had an important impact in the fields of food, environment, and healthcare. Electrochemical analysis is considered to be the simplest and fastest method for the detection of small biomolecules.

Hydrogen peroxide (H₂O₂) is one of the most abundant reactive oxygen species and plays a key role in biological systems. Excessive levels of H₂O₂ in human body fluids are considered to be an indicator of several diseases, such as neurological disorders, cancer, tumors, cardiovascular diseases, Parkinson's disease, Alzheimer's disease. The development of high performance H₂O₂ sensors is of great importance in the biomedical field. Chen et al. [33] synthesized Cu-BHT films for the detection of H₂O₂. The reaction path of H₂O₂ on the surface of the Cu-BHT film is that the H₂O₂ molecule is first adsorbed on the active site and then dissociates into a hydroxyl group, which is also adsorbed on the active site. Next, one of the hydroxyl groups is desorbed from the adsorption site, and the adsorbed hydroxyl group reacts with a protonated hydrogen atom to produce an H₂O molecule adsorbed on the active site, and the catalyst substrate is restored to its initial state after the desorption of the H₂O molecule. The reaction paths of H₂O₂ on the surface of Cu-BHT indicate that the number of ideal active sites on the surface of Cu-BHT films directly affects their H₂O₂ sensing performance. BS-Cu-BHT lower side surface synapse-like structure-induced crystal defects (i.e., ts-Cu sites) act as nanoenzymes, which are important for improving the sensing performance. The BS-Cu-BHT-based sensor had a LOD of 0.08 µmol/L for H₂O₂ and a sensitivity of about 257 µA L mmol⁻¹ cm⁻² (Fig. 10A). To date, electrochemical sensors utilizing CMOFs for the detection of H₂O₂ can be meticulously analyzed through sophisticated electrochemical impedance spectroscopy (EIS) techniques. EIS is an electrochemical analysis technique that obtains impedance spectra by applying a small amplitude alternating current potential perturbation and measuring the system's response. This method can analyze charge transfer and mass transport processes, identifying different stages of electrochemical kinetic behavior. By applying a sinusoidal voltage and measuring the resulting current, the system's impedance is calculated, including both the real part (resistance) and the imaginary part (reactance). EIS is non-invasive in its operation, suitable for delicate and sensitive materials, and capable of accurately measuring minute impedance changes, thereby providing a deep understanding of electrochemical processes and mechanisms. It is widely used in electrochemical research and device optimization. Huang et al. [58] fabricated a sensor for the detection of H₂O₂ using nanohybridised Au-NPs/Cu-HHTP-NSs/GCE modified electrodes. H₂O₂ molecules were absorbed by the surface of Au-NPs and then dissociated into OH. Due to the instability of Au(OH), the surface active sites could be regenerated during the electrochemical reduction step. Meanwhile, the Cu(Ⅱ)-O₄ ligand nodes were partially reduced to Cu(Ⅰ)-O₄ during the electrochemical treatment of Cu-O₄, and the generated Cu(Ⅰ)-O₄ nodes were oxidised back to Cu(Ⅱ)-O₄ in the presence of H₂O₂. The EIS curve indicates that Au-NPs/Cu-HHTP-NSs significantly enhance electron transfer in redox reactions, thereby improving their conductivity performance. Thanks to the synergistic effect of the ultrathin Cu-HHTP-NSs and the high density of ultrafine Au-NPs on them, the modified electrode exhibited outstanding performance on the H₂O₂ showed excellent sensing performance. The reduction current increased linearly with the addition of H₂O₂, indicating the high electrocatalytic activity of Au-NPs/Cu-HHTP-NSs towards H₂O₂. The sensor, with a LOD of 5.6 nmol/L and a sensitivity of 188.1 µA L mmol⁻¹ cm⁻², was applied to track H₂O₂ released from different human colon cells in real time and can discriminate colon cancer cells from normal colon epithelial cells (Fig. 10B). Besides EIS, electrochemical sensors based on CMOFs can also be analyzed using linear sweep voltammetry (LSV) techniques for detecting H₂O₂. LSV utilizes a working electrode as a probe, applying a linearly varying potential signal as a scanning signal, and using the collected current signal as feedback to achieve qualitative and quantitative analysis of substances through scanning. The principle of LSV is similar to CV, but it lacks a reverse scan step, thereby obtaining an LSV curve. The Cu-BHT film prepared by Luo et al. [32] showed excellent performance in H₂O₂ electrocatalytic sensing with a high sensitivity of 479.56 µA L mmol⁻¹ cm⁻² in the high concentration range (0.1–50 mmol/L) and a LOD of 16.5 nmol/L. Most H₂O₂ sensors are tested under inert atmospheres or nitrogen to avoid interference from oxygen reduction reactions (ORR) in environments with similar reduction potentials. The LSV curve on Cu-BHT membrane shows that its optimal working potential is higher than the onset potential of ORR, effectively preventing overlap between the reduction potential of H₂O₂ and ORR. Wang et al. [47] used Cu-hemin MOF/CS-rGO to construct an electrochemical sensor for H₂O₂ with a wide linear range (0.065–410 mmol/L) and low LOD (0.019 mmol/L). At present, relatively few studies have been carried out on CMOF-based electrochemical sensors for the detection of H₂O₂ in food. However, H₂O₂ residues may be present in foods (including nutraceuticals) because it is often added by food processors to processed legumes, pasta, etc. for sterilisation and bleaching. According to food hygiene standards, H₂O₂ residues should not be detectable in food. As the boiling point of H₂O₂ is as high as 152 ℃, H₂O₂ can remain in food even after cooking and boiling. Long-term consumption of food containing H₂O₂ residues may be harmful to human health. Therefore, the development of a CMOFs-based electrochemical sensor with high sensitivity, good selectivity and easy operation for the detection of H₂O₂ residues in food is of great importance for ensuring food safety.

Glucose (Glu) is an important component of the body's physiological fluids and its levels are critical to the body's metabolism. High glucose levels can lead to diabetes, which is a serious threat to human health. Therefore, electrochemical sensing to detect glucose is of great importance. Enzyme-based electrochemical sensors have good sensitivity and selectivity, but their high cost, poor immobilisation ability and instability limit their widespread application. To overcome these problems, enzyme-free electrochemical glucose sensors have been developed. Compared with enzyme-based sensors, enzyme-free electrochemical sensors have the advantages of long lifetime, low cost, good stability, simple operation and easy portability. Therefore, the development of an enzyme-free electrochemical sensor with excellent performance is essential.

Currently, CMOFs-based electrochemical sensors provide an effective solution for continuous glucose monitoring due to their fast, sensitive and selective characteristics. For diabetics, effective management of their condition is essential to improve their quality of life. Several important diabetes management strategies include monitoring blood glucose levels, food type and carbohydrate intake, insulin levels and vital signs. By monitoring blood glucose profiles, one can have better control of blood glucose status. The following sensors were successfully used to detect glucose levels in serum, e.g., Zhang et al. [93] prepared CuNi/C electrodes for use as enzyme-free glucose sensors by electrodepositing copper nanoparticles on a nickel-based MOF. The active sites on the electrode were converted from Ni and Cu to Ni³⁺ and Cu³⁺ and then to Ni and Cu, respectively, during the response process. In addition, the formed Cu(Ⅲ) and Ni(Ⅲ) were used as catalysts for the detection of glucose, which was oxidised to gluconolactone, leading to an increase in peak current. The sensor had a high sensitivity of 17.12 µA L mmol⁻¹ cm⁻² for glucose detection with a low LOD of 66.67 nmol/L and a wide linear range (0.20–2.72 mmol/L) to detect similar values of glucose concentration in human serum samples (Fig. 11A). The enzyme-free electrochemical sensor Cu-MOF/CF prepared by Hu et al. [29] showed an ultra-low LOD of 0.076 µmol/L and a strong sensitivity of 30,030 µA L mmol⁻¹ cm⁻² over a wide concentration range (0.001–0.95 mmol/L). The Cu-MOF exhibited excellent electrocatalytic activity for glucose oxidation under alkaline conditions. The glucose concentration in human serum samples was determined using Cu-MOF/CF, and the quantitative values were almost comparable to those of commercial glucose meters. The standard deviation was less than 0.22 and the RSD was less than 3.44%. The sensor is therefore accurate and reliable. Zhou et al. [94] synthesised [Mn₂{Ni(C₂S₂(C₆H₄COO)₂)₂}(H₂O)₂]·2DMF (1, DMF = N,N-dimethylformamide) and prepared 1-CF as an enzyme-free glucose sensor. The multiple redox states of [NiS₄] allow glucose to be oxidised to gluconolactone by the [NiS₄] centre in the high oxidation state. The sensor has a high sensitivity of 27.9 A L mmol⁻¹ cm⁻², a wide linear detection range of 2.0 × 10⁻⁶–2.0 × 10⁻³ mol/L and a low LOD of 1.0 × 10⁻⁷ mol/L. Chen et al. [95] prepared an enzyme-free glucose sensor based on conductive Ni₃(HITP)₂ MOF with good electrocatalytic activity for glucose oxidation, which showed good linearity in the range of 0–10 mmol/L and can be used for continuous blood glucose monitoring.

As blood glucose levels are closely linked to food intake and daily activities, checking the glucose level of drinks before consuming them can be an important tool in managing diabetes. Knowing the glucose level in beverages can help people with diabetes to better control their blood glucose levels and avoid fluctuations in blood glucose levels, thereby improving their quality of life. It is therefore important to monitor the glucose level in drinks as part of your diet. The Ni-MOF/RGO/CF electrode prepared by Dong et al. [49] has high electrocatalytic activity for glucose. During glucose detection, Ni²⁺ was first converted to Ni³⁺, then Ni³⁺ was converted to Ni²⁺, and glucose was converted to gluconolactone, and the current response was enhanced with increasing glucose concentration. The sensor detected glucose with high sensitivity (852 µA L mmol⁻¹ cm⁻²), wide linear range (6 µmol/L − 2.09 mmol/L) and low LOD (0.6 µmol/L). The glucose level in orange juice samples was determined with this sensor with a relative standard deviation of 3.6%.

CMOFs-based electrochemical sensors have been successfully developed for the detection of glucose levels in both human serum samples and beverages. The range of applications of such sensors provides a more convenient and comprehensive monitoring tool for diabetic patients, contributing to better control of blood glucose levels and improved quality of life. Qiao et al. [39] prepared an enzyme-free electrochemical sensor for glucose detection based on conductive Ni-MOF. Ni-MOF can efficiently catalyse the oxidation of glucose in alkaline media with a response time shorter than 3 s, a low LOD as low as 0.66 µmol/L, and a high sensitivity as high as 21,744 µA L mmol⁻¹ cm⁻². This sensor can detect glucose levels in human serum and peach juice. In the detection of human serum samples, hospital measurements were compared with conductive Ni-MOF measurements with a RSD of less than 4% and a deviation of less than 0.20 mmol/L. Qiao et al. [96] used a three-dimensional Ni-MOF NSAs/CC electrode to fabricate a sensor for the detection of glucose. Glucose was electrooxidised in alkaline solution using Ni-MOF NSAs/CC as a non-noble metal catalyst with a sensitivity of 13,428.89 µA L mmol⁻¹ cm⁻², a LOD as low as 0.57 mmol/L and a wide linear range of 0.001–7 mmol/L. Ni-MOF NSAs/CC showed good catalytic activity in human serum samples. In addition, when different concentrations of glucose were added to the pulsatile beverage, there was a linear relationship between the glucose concentration and the current value. An enzyme-free glucose sensor Ni/Co(HHTP)MOF/CC was prepared by Xu et al. [97] Due to the synergistic catalytic effect of the bimetal on glucose, the sensor exhibited a linear detection range of 0.3 µmol/L−2.312 mmol/L for glucose with a LOD of 100 nmol/L, a fast response time of 2 s and a sensitivity of 3250 µA L mmol⁻¹ cm⁻² and was successfully used to detect glucose levels in serum and beverages.

However, the widespread use of CMOFs-based electrochemical sensors for the detection of glucose levels in human serum samples has been somewhat limited due to the discomfort and pain associated with invasive finger pricking. Therefore, sweat has become ideal for continuous non-invasive glucose monitoring. Sweat is mainly secreted by endocrine sweat glands to maintain the body's heat balance and contains many of the same biomolecules as blood, such as glucose. By monitoring glucose levels in sweat, non-invasive blood glucose monitoring can be achieved, improving patient comfort and compliance. Shu et al. [98] fabricated Ni-Co MOF/Ag/rGO/PU (NCGP) fibre electrodes for continuous monitoring of sweat glucose levels using a modified wet spinning technique with reduced graphene oxide/polyurethane (rGO/PU) prepared using capillary templates and coated with conductive silver adhesive and solvent-thermal synthesised Ni-Co MOF nanosheets. Due to the large specific surface area and high catalytic activity of Ni-Co MOF, the NCGP fibre electrode has excellent electrocatalytic activity compared to rGO/PU and Ag/rGO/PU fibre electrodes, which greatly improves its electrochemical performance for glucose detection. The oxidation current of the enzyme-free glucose sensor prepared based on the NCGP fiber electrode increased with the increase of glucose concentration, indicating that glucose was readily oxidised on the Ni-Co MOF surface over a wide range of concentrations. The redox peaks can be attributed to the redox of nickel and cobalt, and the oxidation of glucose to gluconolactone leads to an increase in the anodic current. The sensor detected glucose with a sensitivity of 425.9 µA L mmol⁻¹ cm⁻² and a linear range of 10 µmol/L−0.66 mmol/L (Fig. 11B).

Wearable electrochemical sensors can be used to non-invasively detect glucose and other key diabetes biomarkers in various biological fluids (e.g., sweat, tears, and saliva) and can be integrated with smart mobile devices. As a result, such sensors are able to monitor blood glucose levels in real time without the need for finger prick blood tests, thus avoiding discomfort. However, relatively little research and development has been done on CMOFs-based electrochemical sensors for detecting glucose levels in sweat, tears or saliva, and further research and improvements are still needed. The primary reasons are as follows: (1) The preparation of CMOFs materials is complex and costly, particularly for large-scale applications, where stability and consistency are also challenging. There is a need to develop simpler and more cost-effective synthesis methods and optimize processes, such as adopting green chemistry or renewable resources. (2) The complex composition of biological fluids and interfering substances affect the selectivity and sensitivity of sensors. Enhancing selectivity and anti-interference capability can be achieved through functional modifications or multi-component composite material designs, using molecular recognition elements or selective membranes to cover the sensor surface and exclude interference. (3) CMOFs must possess good biocompatibility and non-toxicity, but some components may have adverse effects. Further research on surface modification and functionalization techniques is required, including the introduction of biocompatible polymers or natural material coatings to reduce potential toxicity. Addressing these issues can accelerate the application and development of CMOFs electrochemical sensors for glucose detection in biological fluids.

Ascorbic acid (AA), also known as vitamin C, is an essential nutrient for humans and acts as an anti-scorbutic agent. AA can function as an antioxidant to effectively eliminate free radicals in the body, thereby reducing the incidence of cancer. It can also prevent the production of toxic substances by inhibiting peroxidation, maintain the activity of enzymes within the body, and plays a significant role in biological metabolism. For these reasons, quantitative analysis of AA is meaningful. As demonstrated in Fig. 12, Yang and colleagues [99] have developed a wearable and breathable wireless health monitoring sweat sensor by integrating a layered thin-film electrode based on Ni₃HHTP₂ onto a flexible nanocellulose substrate. The sensing mechanism works as follows: Initially, *OH (* denotes the catalytic substrate Ni₃HHTP₂) is formed. ^•OH combines with the catalytic substrate, and then one H atom from AA is transferred to *OH via an electron-proton coupled transfer process, resulting in the formation of *H₂O. This exposes the free active sites of the CMOF to the desorption of water. When OH is bound at the free active sites, *OH is regenerated, and another H atom from AA is transferred to *OH, producing *H₂O. Finally, the catalytic substrate is restored to its original state, and AA is oxidized as the second H₂O molecule is desorbed. The composition of the layered thin-film sensor includes a cellulose layer, CMOF, electrode layer, and insulating layer. The Cr (5 nm)/Au (75 nm) electrode layer connection is encapsulated by the insulating layer to achieve anti-fouling and ensure long-term usability of the sensor. The cellulose layer uses a lightweight, porous bacterial nanocellulose (BNC) film, which can adhere to moist skin, providing comfort to the wearer. Combining the strong catalytic activity and highly porous structure of CMOF with the superior mechanical strength, high permeability, and skin compatibility of nanocellulose, the wet-adhesion epidermal sweat sensor exhibits excellent anti-interference properties, recyclability, mechanical performance, and permeability. Moreover, it shows a good linear relationship between current intensity and AA concentration over a wide concentration range of 10–1190 µmol/L. Wang and others [40] synthesized conductive compound Ni₃(HITP)₂ nanorods with high crystallinity and based on Ni₃(HITP)₂, developed an enzyme-free sensor for AA detection. Owing to the synergistic effect of high-activity Ni-N₄ catalytic sites in the nanorods, this sensor exhibits good catalytic activity for the electrocatalytic analysis of AA in alkaline media, with a wide linear range (2–200 µmol/L), high sensitivity (0.814 µA L mmol⁻¹ cm⁻²), and low LOD (1 µmol/L). Currently, research on CMOF-based electrochemical sensors for AA detection is relatively scarce. Therefore, to further advance the rapid, sensitive, and real-time monitoring of AA, we need to intensify the development of CMOF-based wearable electrochemical sensors. Such sensors will help meet the growing demand for health monitoring and improve the quality of life for people.

Abnormal dopamine (DA) levels can have serious health consequences and lead to a variety of diseases (e.g., depression, attention deficit hyperactivity disorder, schizophrenia, and Parkinson's disease). Wang et al. [61] fabricated a sensor by modifying carbon fiber electrodes with MOFs deposited on gold nano leaves (Au/RP1/Ni₃(HHTP)₂). The conjugated molecular wire RP1 facilitates the heterogeneous electron transfer of DA from the MOF layer to the electrode surface. Au/RP1/Ni₃HHTP₂ provides abundant electrocatalytic sites for the electron transfer of DA on the electrode surface, which greatly improves the sensitivity of DA detection. The sensor exhibited good electrocatalytic activity and selectivity for DA with good linearity in the range of 0.004–0.4 µmol/L and a LOD of 1 nmol/L and was successfully applied to the in vivo monitoring of DA in the brain of Parkinson's disease (PD) mice (Fig. 13A). Huang et al. [100] combined MOF-525 and PEDOT NT as a high-efficiency electrochemical sensor, in which MOF-525 acted as an electrocatalytic surface and PEDOT NT acted as a charge collector, which improved the charge transfer path between the MOF-525 regions and increased the electrochemical active sites. The linear concentration range of DA detection by this sensor was 2 × 10⁻⁶ − 270 × 10⁻⁶ mol/L, and the LOD was 0.04 × 10⁻⁶ mol/L. In addition, real-time determination of DA released from live rat pheochromocytoma cells was achieved. If the interfering analyte also produces a sufficiently sensitive signal at the electrode, discriminatory detection of two or more analytes can be performed simultaneously. Michael et al. [101] prepared sensors by drop-casting Ni₃HHTP₂ dispersed in water directly onto the top of a glassy carbon electrode (GCE) for voltammetric sensing of neurochemicals. The presence of electrostatic attraction between Ni₃HHTP₂ and DA accelerates electron transfer during oxidation, thereby enhancing the voltammetric response. The sensor was able to detect DA over a wide concentration range (40 nmol/L−200 µmol/L) of 6 ± 11 nm for DA and 40 ± 17 nmol/L for 5-HT (Fig. 13B). Wang et al. [54] fabricated an electrochemical sensor using an electrode modified with a Mn-BDC@MWCNT complex, which could promote rapid electron transfer between the redox probe and the electrode-modified material. The sensor had a wide linear detection range (0.1–1150, 0.01–500 and 0.02–1100 µmol/L for AA, DA and UA, respectively) and low LOD (0.01, 0.002 and 0.005 µmol/L for AA, DA and UA, respectively). The Cu-MOF/HNTs/rGO modified GC electrode prepared by Devaraj et al. [50] showed excellent electrochemical signal response for DA and paracetamol with a wide linear range of 0.1–130 µmol/L and 0.5–250 µmol/L for DA and paracetamol, respectively, and LOD of 0.03 µmol/L and 0.15 µmol/L. Changjoon et al. [102] fabricated a CMOF DGFET sensor with a linear detection range of 10⁻⁸−10⁻³ mol/L for DA, and catecholamines could be detected up to 10⁻⁸ mol/L with high sensitivity. Chen et al. [103] synthesized N-Cu-MOFs with a linear detection range of 10⁻⁸−10⁻³ mol/L for DA and sulfonamide (SA), respectively, and a wide linear range of 0.50 nmol/L−1.78 mmol/L with low LOD (0.15 nmol/L) and 0.01–58.3 µmol/L with low LOD (0.003 µmol/L), respectively. At present, CMOFs-based electrochemical sensors for DA detection need to be further improved before they can be applied in practice. For example, CMOF-based sensors may respond to other similar molecules, such as catecholamines. Enhancing selectivity for DA can be achieved by functionalizing the MOF surfaces or introducing selective recognition groups. In real sample analysis, complex matrices may interfere with the sensor's detection accuracy. Therefore, using microfluidic technology for sample pretreatment can improve the sensor's anti-interference capability.

In addition to the above substances, a number of other small biomolecules can be successfully detected by CMOF-based electrochemical sensors. In recent years, diclozepam has grown rapidly in popularity around the world and has become a major problem in the illicit drug market. Criminals surreptitiously add these drugs to drinks, capsules or pills, causing effects such as rapid drowsiness, hallucinations and short-term memory loss, making it easier to commit criminal acts. To address these problems, efforts have been made to develop various strategies that can detect diclazepam, but a number of limitations, such as high cost and specialized operations, have also limited the use of these methods. Therefore, it is particularly important to develop a method for the detection of diclazepam with high sensitivity and specificity. A novel porous MOF/COF complex, Cu₃(HHTP)₂/PTCA-COF, which can be used as an ECL sensor for the selective determination of diclazepam, has been prepared by An et al. [104]. Its excellent ECL performance is attributed to the properties of the porous MOF/COF composites and the excellent synergy between them. On the one hand, the complex possesses both the ECL properties of PTCA-COF at 520 nm and Cu₃(HHTP)₂ at 600 nm, which do not interfere with each other, thus significantly enhancing the ECL strength of the complex. On the other hand, the excellent electrical conductivity of Cu₃(HHTP)₂ facilitates rapid charge transfer within the framework, which promotes electrochemical activation of the ECL luminophores. At higher potentials, K₂S₂O₈ becomes unstable after receiving electrons and generates SO₄^•− radicals through a deprotonation process. At this point, the PTCA-COF on the electrode surface is reduced to the highly active PTCA-COF^•−. Subsequently, PTCA-COF^•− reacts with SO₄^•− to form the excited state PTCA-COF*. Finally, when the excited PTCA-COF* returns to the ground state, it releases energy, which is observed as an electrochemiluminescence signal. The porous structure of the complex ensures a strong physical adsorption capacity, enabling efficient adsorption of analytes. Through π-π interactions, diclazepam adsorbs well on the porous-structured MOF/COF complex and selectively bursts the ECL signal of PTCA-COF, resulting in sensitive detection. The ECL sensor has a wide detection range from 1.0 × 10^–13 g/L to 1.0 × 10^–8 g/L. The ECL sensor has a wide detection range from 1.0 × 10^–13 g/L to 1.0 × 10^–8 g/L, with a LOD as low as 2.6 × 10^–14 g/L. This study demonstrates that Cu₃(HHTP)₂ effectively enhances the ECL response of PTCA-COF by increasing the system's electron transfer efficiency and the quantity of luminophores, showcasing its potential application value in the field of electrochemiluminescence. Tryptophan (Trp) is an essential amino acid that plays a crucial role in a wide range of metabolic functions, and tryptophan levels can be used to diagnose various types of metabolic disorders and the symptoms associated with these diseases. Huang et al. [105] fabricated a sensitive sensor for the electrochemical detection of tryptophan based on three-dimensional peony flower-like bimetallic CMOFs (Co-Ni-MOFs). The bimetallic Co-Ni-MOFs exhibited good electrochemical performance due to the synergistic effect of Ni²⁺ and Co²⁺ ions. The LOD of tryptophan at the Co-Ni-MOFs-modified electrode was 8.7 nmol/L with a linear range of 10 nmol/L − 300 µmol/L, and the sensor was successfully applied to the determination of tryptophan content in plasma of cadmium-poisoned mice. MicroRNA-141 (miRNA-141) is closely related to the early pathological development of various cancers, and its detection is helpful for the early diagnosis of cancer. Yang et al. [106] prepared an ultrasensitive electrochemical sensor based on NiCo-HHTP nanorods for the detection of microRNA-141, with a linear range of 1 fmol/L − 10 nmol/L and a detection limit of 0.69 fmol/L.

In summary, despite certain progress in the study of small molecule detection using CMOF-based electrochemical sensors, there remain areas for improvement. For example, their application scenarios are relatively limited, facing some challenges in practical use, and there is comparatively less research on their application in wearable devices. Therefore, future research needs to focus on further optimizing sensor performance, expanding their application scenarios, and exploring their use in wearable devices to meet a broader range of practical needs.

3.4.2. Biomacromolecules detection

Biomacromolecules, such as proteins, nucleic acids, and polysaccharides, are crucial components of living organisms. Abnormal levels of these biomacromolecules in the body often indicate the onset of diseases. Hence, biomacromolecules are extensively utilized as biomarkers for diseases. Disease-related biomacromolecules can objectively assess the pathogenic process and the pharmacological response after intervention, and are widely used in disease identification, classification, early diagnosis, and prevention. The quantitative detection of biomacromolecules is of significant clinical value for early physiological dysfunction and for tracking disease progression. The use of CMOF-based electrochemical sensors, with their high sensitivity, accuracy, and selectivity in detecting biomacromolecules, plays a positive role in the rapid development of biomedicine.

The application of CMOFs in DNA detection leverages their unique properties for research and practical use in this field. By combining CMOFs with DNA probes, a highly sensitive and selective detection platform can be constructed. In this method, CMOFs serve as carriers, providing excellent conductivity and a large specific surface area, which enhance the electrochemical signal and improve detection sensitivity. Additionally, through the rational design of the DNA probe sequences and structures, specific recognition and detection of target DNA can be achieved. This CMOF-based DNA detection method holds broad application prospects in gene diagnostics, pathogen detection, and environmental monitoring. It contributes to improved detection accuracy and efficiency, thereby promoting advancements in biomedical and environmental sciences. The development of a simple, efficient and rapid method for the detection of circulating tumor DNA (ctDNA) has development potential in the early detection, treatment and prognosis of tumors. Liu et al. [62] synthesized 2D conductive Ni-CAT composed of highly conjugated tricatecholate, HHTP, with Ni(Ⅱ) ions by a one-step hydrothermal method. The Ni-CAT/CB complex-modified AuNPs were then electrodeposited on the surface of PPGE to prepare AuNPs/Ni-catecholates/carbon black/polarized pencil graphite electrodes (AuNPs/Ni-CAT/CB/PPGE). AuNPs were deposited on the surface of the electrodes, providing binding sites for probe DNA (pDNA), and after the pDNA was bound, the binding sites were closed to prevent non-specific adsorption. The base-complementary coordination of ctDNA with pDNA has an effect on electron transfer at the electrode, resulting in a decrease in current. The AuNPs/Ni-CAT/CB/PPGE sensor was used for the label-free detection of ctDNA, with a total detection time of only 30 min and a good linear response to ctDNA over a wide concentration range of 1 fmol/L−1 µmol/L, with an LOD as low as 0.32 fmol/L, the sensor can be applied to the highly sensitive determination of ctDNA in serum samples. This is the first time that CMOFs have been used for the detection of biomolecules, taking full advantage of their excellent properties of electrical conductivity and specific surface area (Fig. 14A). The stability of CMOF materials may be affected by environmental conditions such as humidity and temperature, posing challenges to their reliability in long-term use and practical scenarios. Although CMOFs exhibit excellent performance in laboratory settings, their relatively high cost, especially for large-scale applications, can be a limiting factor. In practical applications, establishing uniform standards and protocols is necessary to ensure the comparability and reproducibility of results across different laboratories or equipment. With advances in materials science and nanotechnology, improvements in the synthesis methods of CMOFs are expected to enhance their stability and electrochemical performance, thereby promoting their application in DNA detection. Future research may focus on designing multifunctional CMOF materials, such as those integrating fluorescent or magnetic markers, to expand their applications in biosensing and imaging. Beyond DNA detection, CMOFs are also expected to extend to the detection of other biomolecules such as RNA and proteins, further broadening their application scope and market potential. Overall, while CMOF-based DNA detection methods face some technical challenges, their high sensitivity, specificity, and potential for multifunctional design offer significant prospects in biomedical and environmental detection fields. With technological advancements and growing application needs, it is anticipated that CMOFs will gradually overcome current challenges and achieve broader application and commercialization.

CMOFs combine the advantages of organic molecules and metal ions, featuring a high specific surface area and a rich pore structure conducive to the capture and recognition of proteases. Additionally, the adjustable pore sizes of CMOFs allow for the selective identification and capture of protease molecules of specific sizes, enhancing detection selectivity. CMOFs can convert the recognition process of proteases into electrical signals through electrochemical sensors. When proteases react with specific substrates, the degradation of these substrates causes changes in the electrochemical properties on the surface of CMOFs. These changes can be detected through electrochemical signals (such as current and voltage), thereby achieving high-sensitivity detection of proteases. The surface of CMOFs can undergo functional modifications, such as introducing specific recognition groups or signal amplification components, further enhancing their detection performance. For instance, by incorporating fluorescent probes or nanoparticles, higher sensitivity and multiple signal modes for protease detection can be achieved. CMOF-based protease detection technology holds significant promise in clinical diagnostics, drug screening, and disease monitoring. Particularly in real-time and rapid detection, CMOF materials demonstrate notable advantages and are expected to drive the further development of protease detection technologies. Thrombin (TB) is a serine protease that regulates physiological and pathological processes such as coagulation, congestion and inflammation. Zhang et al. [107] Using the conductive metal-organic framework Ni₃(HITP)₂ as a support and grafting Ru(bpydc)₃⁴⁻ (H₂bpydc = 2,2′-bipyridine-4,4′-dicarboxylic acid) into the pores of Ni₃(HITP)₂, a high-performance metal-organic framework-based ECL material Ru@Ni₃(HITP)₂ with electrical conductivity and confined enhanced ECL was successfully constructed. Compared with Ru@Cu₃(HITP)₂ and Ru@Co₃(HITP)₂, which have relatively lower electrical conductivity, the ECL strength of Ru@Ni₃(HITP)₂ was significantly enhanced by about 6.76-fold and 18.8-fold, respectively. In addition, the hydrophobic and porous Ni₃(HITP)₂ not only effectively enriched the lipophilic tripropylamine (TPrA) co-reactant to improve the electrochemical oxidation efficiency of TPrA, but also provided a conductive reaction microenvironment to facilitate the ECL reaction between Ru(bpydc)₃⁴⁻ intermediate and TPrA in the confined space, resulting in a significant confined enhanced ECL. Considering the excellent ECL performance of Ru@Ni₃(HITP)₂, an ultrasensitive ECL sensor was prepared based on the Ru@Ni₃(HITP)₂ ECL indicator combined with a nucleic acid exonuclease I-assisted target cycling amplification strategy for TB detection, which exhibited a wide linear range of 1 fmol/L − 1 nmol/L and a low LOD of 0.62 fmol/L (Fig. 14B). Despite the many advantages of CMOF-based protease detection technology, there are still numerous challenges in practical applications. (1) Although CMOFs have tunable pore structures, ensuring high selectivity and specificity for specific proteases during actual detection remains a challenge. The presence of other biomolecules or interfering substances may affect the detection results. (2) Despite the good electrochemical properties of CMOFs, further optimization is needed for signal amplification and lowering the detection limit in ultra-low concentration protease detection. Effectively amplifying detection signals and reducing background noise to achieve lower detection limits is a significant challenge. (3) In clinical applications, the biocompatibility and safety of CMOFs are crucial. It is essential to ensure their stability and non-toxicity within biological systems to avoid adverse effects on the human body. Overall, although CMOF-based protease detection technology holds broad application prospects, overcoming the aforementioned challenges is necessary for practical applications. Future research should focus on material optimization, innovation in detection technologies, and addressing practical application issues to drive the development of this field.

Although there have been some breakthroughs and progress in the detection of biomacromolecules using CMOF-based electrochemical sensors, their application remains relatively limited. This may be due to the need for further research on the sensing mechanisms for biomacromolecules, or because the performance of CMOF-based electrochemical sensors for biomacromolecule detection requires further enhancement. While CMOFs exhibit exceptional catalytic activity, high porosity, adjustable topological structures, and ease of functionalization, their application in biomacromolecule detection necessitates more extensive research and exploration. Therefore, future efforts should focus on further improving and optimizing CMOF-based electrochemical sensors to enhance their performance and application scope in biomacromolecule detection.

4. Conclusion and outlook

As a novel material in the field of electrochemical sensors, CMOFs have shown significant potential and advantages. They combine the high specific surface area, porosity, and the easily adjustable structure and functionality of MOFs with excellent conductivity, offering a robust platform for constructing high-performance electrochemical sensors. This review discusses the synthesis, functionalization, and applications of CMOFs in electrochemical sensing, with a focus on the latest advancements in the detection of ions, organic pollutants, gases, and biomolecules. Despite the enormous potential of CMOFs in the realm of electrochemical sensing, the rationality of design, application expansion, and commercialization transition remain key issues that researchers need to address. Electrochemical sensors based on CMOFs currently face the following challenges:

(1) Although CMOFs possess higher catalytic activity due to their high-density metal nodes and abundant active sites, the structural diversity of reported CMOFs is significantly lacking compared to traditional MOFs, and there is a need to develop structures with novel functional properties. The lack of rational and effective synthesis strategies to construct different CMOF structures is a bottleneck. There is an urgent need to develop new ligands and metal coordination modes to achieve a wide range of tunability in CMOFs' structures and properties. Furthermore, the strategy of combining CMOFs with nanozymes merits further exploration. The integration of CMOFs with nanozymes can significantly enhance the catalytic activity of the composite. Due to the high catalytic activity and unique structural and electrical properties of both CMOFs and nanozymes, electrochemical sensors exhibit superior performance under this synergistic interaction.

(2) While CMOFs exhibit unique electrochemical properties, their chemical and thermal stability often do not match those of traditional inorganic conductive materials. Under extreme conditions, such as strong acid/base environments or high temperatures, CMOFs may undergo structural degradation, leading to a decline in sensing performance. Moreover, considering that some CMOFs are prone to disintegration in aqueous media, which is not conducive to long-term, continuous monitoring, it is necessary to optimize CMOFs' ligands by introducing a variety of functional groups to alter charge distribution and conductivity while enhancing stability. Design CMOFs with strong π-π stacking and metal-ligand bonding strength to enhance their structural stability. By controlling the synthesis conditions of CMOFs, such as temperature, solvent, and reaction time, a high-crystallinity and low-defect structure can be achieved, thereby improving their thermodynamic stability.

(3) In the development process of electrochemical sensors, optimizing selectivity, sensitivity, response time, and ensuring biocompatibility present multidimensional challenges, especially for CMOF-based sensing systems. To enhance these performance indicators for CMOF electrochemical sensors, researchers must delve into material design and sensing mechanisms, continuously innovating and exploring within this field. The application of CMOFs in the detection of biomolecules is still in its infancy, requiring further research to elucidate their sensing mechanisms and expand their application areas. When developing environmental monitoring and biosensing applications, the biocompatibility and potential ecological effects of CMOFs should be seriously considered to ensure their safety and reliability in practical applications. By combining CMOFs with biorecognition molecules such as antigens, antibodies, and aptamers, high specificity recognition of target analytes can be achieved, thereby enhancing the selectivity, sensitivity, and biocompatibility of the sensors. Additionally, exploring the integration of CMOFs with other cutting-edge materials or technologies, such as nanotechnology, microfluidic systems, and sensor arrays, can further enhance sensor performance.

(4) Currently, although the electrical conductivity of CMOFs has been improved, many CMOFs still exhibit lower conductivity compared to traditional conductive materials, limiting their application in high-performance electrochemical sensors. To achieve more efficient electron transport and better sensing performance, enhancing the conductivity of CMOFs remains an important research direction. Addressing this key technical point through doping, post-synthetic modification, or constructing composite materials is urgently needed. Conducting mechanisms have become a critical design principle for CMOFs; however, the charge transfer mechanisms in specific CMOFs may not fully align with practical scenarios. Extensive research is required before fully understanding the charge transfer properties in CMOFs. The effective interface and electron transport efficiency between CMOFs and electrode materials are also crucial factors affecting the performance of electrochemical sensors. Optimizing interface design and improving the charge transfer efficiency between conductive MOFs and electrodes are among the issues that need to be addressed in current research.

(5) Developing reliable large-scale synthesis techniques is a crucial task in transitioning CMOFs from laboratory research to industrial production. Ensuring repeatability across synthesis batches is not only vital for industrial production but also a fundamental requirement for electrochemical sensing applications. Although CMOFs, with their unique topological structures, orderliness, and excellent mechanical properties, have shown great potential for application in constructing nanoscale devices, achieving high-quality and large-scale production of their thin-film materials remains challenging. In practical application environments, the performance of CMOFs may exhibit a declining trend due to the influence of variable factors such as temperature, pH value, mechanical stress, and applied voltage, specifically reflected in device activity and stability, especially when the coordination bonds within CMOFs are weak, making it particularly challenging to ensure the cyclical stability of these devices. Therefore, a series of in-depth studies and optimizations on high-quality, large-scale synthesis methods for CMOF films must be conducted to apply them in electrochemical sensor devices.

(6) The current synthesis processes for CMOFs often involve costly precursors and complex production steps, significantly increasing material costs. To push CMOFs towards the threshold of commercial application, it is urgent to develop more scalable, economical, and efficient preparation methods. As electrochemical sensors find increasingly widespread applications across various fields, processing and analyzing big data, especially in on-site rapid detection and real-time monitoring, has become an urgent technical challenge. This not only requires high-performance sensing materials but also depends on advanced data processing algorithms and system integration capabilities. It is foreseeable that the demand for portable on-site testing (POCT) will continue to grow. With its advantages of easy operation, rapid response, and low-cost production, POCT brings new development opportunities for CMOF-based electrochemical sensors.

In summary, although electrochemical sensors based on CMOFs exhibit broad future application prospects, addressing the above challenges is key to fully realizing their immense potential in the field of electrochemical sensing. Through interdisciplinary collaboration, focusing on research in materials science, electrochemistry, nanotechnology, and computer science, these challenges are expected to be overcome in the future. With the continuous emergence of solutions, electrochemical sensors based on CMOFs are poised to become powerful tools in important areas such as food safety, environmental monitoring, and biomedical diagnostics.

Declaration of competing interest

The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.

CRediT authorship contribution statement

Huili Zhao: Writing – original draft, Investigation, Formal analysis, Conceptualization. Xiao Tan: Investigation, Formal analysis. Huining Chai: Supervision, Resources, Funding acquisition. Lin Hu: Writing – review & editing, Supervision, Resources, Funding acquisition. Hongbo Li: Supervision, Software. Lijun Qu: Supervision, Resources. Xueji Zhang: Supervision, Resources, Funding acquisition. Guangyao Zhang: Writing – review & editing, Supervision, Resources, Project administration, Funding acquisition, Conceptualization.

Acknowledgments

This work was financially supported by the National Natural Science Foundation of China (Nos. 22204089, 52201281, and 22234006), and Natural Science Foundation of Shandong Province (No. ZR2023MB016).