Electrochemical-Based Sensing Platforms for Detection of Glucose and H2O2 by Porous Metal–Organic Frameworks: A Review of Status and Prospects

Establishing enzyme-free sensing assays with great selectivity and sensitivity for glucose and H2O2 detection has been highly required in biological science. In particular, the exploitation of nanomaterials by using noble metals of high conductivity and surface area has been widely investigated to act as selective catalytic agents for molecular recognition in sensing platforms. Several approaches for a straightforward, speedy, selective, and sensitive recognition of glucose and H2O2 were requested. This paper reviews the current progress in electrochemical detection using metal–organic frameworks (MOFs) for H2O2 and glucose recognition. We have reviewed the latest electrochemical sensing assays for in-place detection with priorities including straightforward procedure and manipulation, high sensitivity, varied linear range, and economic prospects. The mentioned sensing assays apply electrochemical systems through a rapid detection time that enables real-time recognition. In profitable fields, the obstacles that have been associated with sample preparation and tool expense can be solved by applying these sensing means. Some parameters, including the impedance, intensity, and potential difference measurement methods have permitted low limit of detections (LODs) and noticeable durations in agricultural, water, and foodstuff samples with high levels of glucose and H2O2.


Introduction
Glucose is the main energy supply source in organisms, and changes in the standard levels of this substance, low or high, may result in diseases [1]. By considering glucose ranges in the blood, diabetes signals in humans can be managed and controlled [2]. Today, diabetes has become a common, chronic, and global health burden disease with fatal consequences [3]. When contrasted with other diseases, it may result in complications such as renal failure, blindness, stroke, and cardiovascular disease. Since diabetes is a chronic disease, monitoring the concentration of blood glucose repeatedly could facilitate the diabetic lifestyle and improve treatment efficiency [4]. A typical reactive oxygen species (ROS), namely, hydrogen peroxide (H 2 O 2 ), has a major role in the foodstuff industry and sensing platforms that have been developed for a considerable period, along with prior research works associated with glucose and H 2 O 2 detection, will be presented to discuss their obstacles and upcoming perspectives. of MOFs made exceptional accomplishments in the electrochemical recognition of glucose, H2O2, and heavy metal ion sensing [24]. In this review, MOFs' general description, assembly, and high-potential employment are demonstrated. In the following, the importance of glucose and H2O2 detection will be emphasized (Scheme 1). Finally, MOFbased electrochemical sensing platforms that have been developed for a considerable period, along with prior research works associated with glucose and H2O2 detection, will be presented to discuss their obstacles and upcoming perspectives. Scheme 1. Graphical representation of the MOF-based sensing platforms for determination of glucose.

MOFs: General Definition and Structure
MOFs are a new kind of microporous compound fabricated from metallic modes that have been connected through organic ligands [25]. The metallic content of inorganic nodes in MOFs represents active sites that play a significant role in assessing their catalytic function [26]. MOFs have received attention because of their high surface areas, highly variegated assembly, customizable chemistry, tunable pore structural design, various structures, ultra-low densities, thermal stability, and simple synthesis routes suitable for chemical and physical applications [27]. They have been extensively employed in the areas of drug delivery, catalysis, gas separation/adsorption, energy storage, and sensors as a result of the aforementioned benefits [28]. MOFs, also known as porous coordination polymers, are 3D-ordered porous materials which, in certain cases, exhibit record-setting internal surface areas [29]. Based on these exclusive properties, the redox-active MOFs demonstrate high potential in electrochemical applications and energy storage. Furthermore, the redox-active activity of MOFs can possibly be applied as an electrochemical sensing stand [30].
Topologically, all MOFs are formed from secondary building units (SBUs) constructed from oxygen atoms and metal ions. Furthermore, organic linkers play a major role in connecting the SBUs within MOFs' framework. The progress of MOFs brought significance to the structural scope since they were assembled via different shapes (squares, triangles, tetrahedrons, and octahedrons) SBUs. Every year, several types of SBUs are attached to organic linkers to synthesize thousands of new MOFs [31]. To modulate chemical functionalities and the crystalline structure of MOFs, inorganic and organic components must be selected wisely [32]. The metallic components of MOFs, metal clusters, and/or isolated metal centers, participate in its catalytic activity. Incorporating MOFs with one or more additional metal centers can increase their specified function [33]. Considering their ultimate properties and structures, MOFs are possibly manufactured via a diverse range of synthetic techniques, such as mechanochemical [34], hydrothermal (solvothermal) [35], slow diffusion [36], electrochemical [37], microwave-assisted heating, and ultrasound [38]. MOFs are prepared in different forms, including nanoparticles, nanospheres, nanorods, and nanosheets.

Electrochemical-Based Sensing Assay for Detection of Glucose
In recent years, electrochemical approaches provided an enlarged potential for the on-site detection of materials through improving speedy analysis and proper miniaturization. Currently, electrochemical methods are increasingly prevalent in sensing studies in comparison with other detective tools, such as spectro-photometric colorimetric and surface plasmon resonance methods. Recently, electrochemical platforms were rapidly established and are used due to their speedy sensing time, high sensitivity, straightforward process, and low cost [39]. Different electrochemical approaches of voltammetric, electrochemiluminescence, amperometric, and impedimetric were employed for this purpose [39]. Nanomaterial-based compounds in electrochemical sensing tools have a promising prospect as a result of their biocompatibility and preserving biological capability during absorption [40]. The overall electrochemical sensing mechanism of glucose is based on glucose oxidation to gluconolactone by applying the reductive form of the electroactive synthesized MOF-based compounds. For instance, Co (III), Cu (III), and Ni (II) are formed on the surface of the nanoparticles. Meanwhile, the oxidation peak current increases, whereas the reduction peak current decreases, owing to the feeding of Co (III), Cu (III), and Ni (II) agents and the formation of Co (II), Cu (II), and Ni agents. The electroactive MOF-based compounds and glucose molecules undergo an electrochemical reaction, releasing electrons and producing electrical signals proportional to the glucose concentration. Table 1 demonstrates various electrochemical-based detecting platforms for the highly sensitive determination of glucose. Wei et al. [41] used NiMn layered double hydroxide (LDH)-based MOF (NiMn-LDH-MOF) material as electrochemical electrode in a sensitive assay of glucose. The NiMn-LDH-MOF was synthesized by one-pot method via directly blending MOF-74, metal nodes, and ammonia. The obtained NiMn-LDH-MOF has excellent electrocatalytic activity for electrochemical oxidation of glucose and the NiMn-LDH-MOF/GCE sensor exhibits a wide linear detection range from 4.9 µM to 2.2 mM, a low detection limit (0.87 µM, S/N = 3), and high sensitivity (0.849 mA mM -1 cm -2 ). Meanwhile, the sensor has good selectivity and reliability for glucose detection in real serum samples, suggesting the potential applicability of the sensor for glucose detection. The more exposed active sites, the introduction of LDHs subunit, and the synergistic effect between Ni and Mn in the NiMn-LDH-MOF are the major factors enhancing the assay performance.
Zeraati et al. [42] established a Ni-MOF electrochemical sensor for glucose recognition. The MOF was manufactured with a mean particle size of 80 nm, significant porosity of 1.14-9.6 nm, and a surface area of 1381 m 2 /g. The amperometric response of the electrode toward glucose was achieved at a steady state in 3 s. The LOD, linear range, and sensitivity for glucose were 0.76 µM (S/N = 3), 1-1600 µM, and 2859.95 µA mM −1 cm −2 (R 2 = 0.9966), respectively. In comparison with non-enzymatic ones, the provided electrode has promising standards to develop a sensor of higher sensitivity and lower LOD. In another work performed by Liu et al. [1], Cu has been doped into a Co-based MOF of a 2D structure to detect glucose and oxygen evolution reaction (OER). Two-dimensional booklike CuCo-MOF was grown in situ on carbon fiber paper (CFP) by a one-step solvothermal reaction, which can be directly used as a general anodic electrocatalytic material for glucose detection and water oxidation. The electrocatalytic glucose recognition had a linear range, high sensitivity, and a low detection limit of 10-1200 µM, 6.861 mA mM −1 cm −2 and 0.12 µM, respectively. For the OER, once the density reached 10 mA cm −2 , the overpotential (Z) was 340 mV, and well stability was preserved for approximately 10 h without current weakening. The 2D MOF structure had an increased potential in the electrocatalytic OER.
A hierarchical 3D nitrogen-doped carbon nanotube anchored bimetallic cobalt copper organic framework (NCNT MOF CoCu) has efficaciously been fabricated through the direct growth method by applying high-temperature carbonization of bimetallic cobalt copper organic structure (MOF CoCu-500) by applying 2-methylimidazole as an effective ligand ( Figure 1A). High-level function for H 2 O 2 and glucose molecules sensing is possessed by the NCNT MOF CoCu nanostructure. The presence of nitrogen-doped carbon in nanotube array form immobilized on the surface of MOF CoCu nanostructure is effectively confirmed by applying the TEM and FE-SEM as depicted in Figure 1B,C. On the other hand, Figure 1D demonstrates the XRD schemas of (a) Co MOF, (b) Cu MOF, and (c) nanocube structures of CoCu MOF. Moreover, to explain the successful fabrication of Cu and Co nanoparticles, the XRD pattern of NCNT MOF CoCu nanostructure is demonstrated in Figure 1D(d). The typical peaks associated with XRD patterns placed at 2θ = 43.7 • and 45.6 • are apportioned to diffraction planes of cubic copper and cobalt, respectively. For electrochemical behavior investigation, Figure 1E explains the cyclic voltammetry (CVs) of (a, b) unmodified GCE (glassy carbon electrode), (c, d) Cu MOF, (e, f) Co MOF, (g, h) nanocube structures of CoCu MOF, (i, j) CoCu-500MOF, and (k, l) the prepared bimetallic NCNT CoCu MOF. Figure 1F shows cyclic voltammograms of the nanostructure related to the bimetallic NCNT CoCu MOF. This research presented a first-rate electrocatalytic presentation for glucose oxidation with a linear range of 0.05 to 2.5 mM, a sensitivity of 1027 µA mM −1 cm −2 , and an LOD of 0.15 µM. In the same way, the NCNT MOF CoCu nanostructure had considerably higher H 2 O 2 function with a linear range, sensitivity, and detection limit of 0.05 to 3.5 mM, 639.5 µA mM −1 cm −2 , and 0.206 µM, respectively. The bimetallic NCNT MOF CoCu nanostructure modified GCE current response retains at least 96% of the original value after 60 days. These results are owed to the synergistic effect between NCNT and bimetallic CoCu in the organic structure. This structure gives highly graphitized carbon, homogeneous nitrogen-doped carbon nanotubes, and a unique hierarchical nanoarchitecture. In addition, as an appropriate probe for H 2 O 2 and glucose detection, the fabricated sensor has been applied in real models [43].
Xu et al. [16] set up an enzyme-free electrochemical-based glucose sensor by applying direct growth of a conductive bimetal by applying HHTP (HHTP = 2,3,6,7,10,11hexahydroxytriphenylene) as an organic linker (Ni/Co(HHTP)) MOF on carbon cloth [Ni/Co(HHTP)MOF/CC] using the hydrothermal technique ( Figure 2A). The mentioned figure schematically demonstrates that the direct sensing mechanism is based on the glucose and gluconolactone electrochemical reaction by considering the reductive form of the electroactive synthesized MOF. The surface area and the pore volumes of the bimetallic MOF were 180.3159 m 2 /g and 0.39 cm 3 /g. This improvement was attributed to the first-rate conductivity between Ni/Co(HHTP)MOF and CC, and the synergic catalytic effect of Ni and Co elements. Additionally, Figure 2B displays that it is shaped by firmly linked units like thick rods with a size of one hundred nanometers. This construction owns a greater surface area and more adsorption sites for highly sensitive determination of glucose sensing than that of the smooth carbon cloth. Many unsettled nanorods could be recognized from the TEM image ( Figure 2C). On the other hand, Figure 2D displays the CVs of the bare CC and the Ni/Co(HHTP)MOF/CC (the ratio of nickel to cobalt is 2:1) with or without 1.0 mM glucose. Electrochemical responses have indicated that the unmodified CC displays that no redox peak seemed apparent in the absence of glucose, and the CV of the bare CC was hardly altered after the addition of glucose, which confirms that the unmodi-fied CC is comparatively inactive in the glucose redox reaction. Furthermore, Figure 2E confirms the amperometric signals of the Ni/Co(HHTP)MOF. In optimum conditions, the Ni/Co(HHTP)MOF/CC has demonstrated high activity with a linear range, low LOD, sensitivity, and fast response of 0.3 µM-2.312 mM, 100 nM (S/N = 3), 3250 µA mM −1 cm −2 , and 2s, respectively. Xu et al. [16] set up an enzyme-free electrochemical-based glucose sensor by applying direct growth of a conductive bimetal by applying HHTP (HHTP = 2,3,6,7,10,11-hexahydroxytriphenylene) as an organic linker (Ni/Co(HHTP)) MOF on carbon cloth [Ni/Co(HHTP)MOF/CC] using the hydrothermal technique ( Figure 2A). The mentioned figure schematically demonstrates that the direct sensing mechanism is based on the glucose and gluconolactone electrochemical reaction by considering the reductive form of the electroactive synthesized MOF. The surface area and the pore volumes of the bimetallic MOF were 180.3159 m 2 /g and 0.39 cm 3 /g. This improvement was attributed to the firstrate conductivity between Ni/Co(HHTP)MOF and CC, and the synergic catalytic effect of Ni and Co elements. Additionally, Figure 2B displays that it is shaped by firmly linked units like thick rods with a size of one hundred nanometers. This construction owns a greater surface area and more adsorption sites for highly sensitive determination of glucose sensing than that of the smooth carbon cloth. Many unsettled nanorods could be recognized from the TEM image ( Figure 2C). On the other hand, Figure 2D displays the CVs of the bare CC and the Ni/Co(HHTP)MOF/CC (the ratio of nickel to cobalt is 2:1) with or without 1.0 mM glucose. Electrochemical responses have indicated that the unmodified CC displays that no redox peak seemed apparent in the absence of glucose, and the CV of the bare CC was hardly altered after the addition of glucose, which confirms that the unmodified CC is comparatively inactive in the glucose redox reaction. Furthermore, Figure  2E confirms the amperometric signals of the Ni/Co(HHTP)MOF. In optimum conditions, the Ni/Co(HHTP)MOF/CC has demonstrated high activity with a linear range, low LOD, sensitivity, and fast response of 0.3 μM-2.312 mM, 100 nM (S/N = 3), 3250 μA mM −1 cm −2 , and 2s, respectively. Recently, Wang et al. [44] successfully provided an efficient modifier agent based on carbon cloth, where a 3D self-supporting NiO-MOF, which used 2,5-dihydroxyterephthalic acid as an organic linker (MOF-74) and NiCo LDH (layered double hydroxide) composite, was prepared. Straightforward electrochemical deposition and hydrothermal processes were used in the synthesis. By applying the unique flower-like 3D framework, the modified electrode showed appropriate electrochemical behavior, where the capacitance and high rate capability were 9.73 F cm −2 of 77.65%, respectively. A high density of 50 mA cm −2 and a capacitance retention rate of 84.09% were achieved after 5000 cycles. In addition, the synthesized tool demonstrated superb power and energy density of 1750 W kg −1 and 22.85 Wh kg −1 , respectively. Furthermore, the fabricated nanocomposite presented a firstrate electrocatalytic performance in detecting glucose, with a linear range of 10 µM-1.1 mM, a low detection limit of 278 nM (S/N = 3), and a high sensitivity of 1699 µA mM −1 cm −2 . However, the modified electrode presented acceptable long-term stability after 35 days, which could be assigned to the high surface area and enhanced conductivity. Here, additional active sites for electrochemical reactions were offered and the ion transport direction was reduced by the synergistic effect of the bimetal Ni-Co. Therefore, the constructed CC@MOF-74(NiO)@NiCo LDH may have a potential application point of view in the area of non-enzymatic glucose sensors and supercapacitors. Biosensors 2023, 13, x FOR PEER REVIEW 9 of 22 Recently, Wang et al. [44] successfully provided an efficient modifier agent based on carbon cloth, where a 3D self-supporting NiO-MOF, which used 2,5-dihydroxyterephthalic acid as an organic linker (MOF-74) and NiCo LDH (layered double hydroxide) composite, was prepared. Straightforward electrochemical deposition and hydrothermal processes were used in the synthesis. By applying the unique flower-like 3D framework, the modified electrode showed appropriate electrochemical behavior, where the capacitance and high rate capability were 9.73 F cm −2 of 77.65%, respectively. A high density of 50 mA cm −2 and a capacitance retention rate of 84.09% were achieved after 5000 cycles. In addition, the synthesized tool demonstrated superb power and energy density of 1750 W kg −1 and 22.85 Wh kg −1 , respectively. Furthermore, the fabricated nanocomposite presented a first-rate electrocatalytic performance in detecting glucose, with a linear range of 10 μM-1.1 mM, a low detection limit of 278 nM (S/N = 3), and a high sensitivity of 1699 μA mM −1 cm −2 . However, the modified electrode presented acceptable long-term stability after 35 days, which could be assigned to the high surface area and enhanced conductivity. Here, additional active sites for electrochemical reactions were offered and the ion transport direction was reduced by the synergistic effect of the bimetal Ni-Co. Therefore, the constructed CC@MOF-74(NiO)@NiCo LDH may have a potential application point of view in the area of non-enzymatic glucose sensors and supercapacitors.
Qiaoand et al. [45] presented the application of a conductive Ni-MOF, which is an on-noble-metal catalyst for proficient glucose electrooxidation in alkaline electrolytes. For glucose detection, this Ni-MOF demonstrated the LOD, stability, and sensitivity of 0.66 μM (S/N = 3), 30 days, and 21,744 μA mM −1 cm −2 , respectively, with a rapid response period of lower than 3 s. In addition, the conductive Ni-MOF exhibits a detection range from 0.001 to 8 mM. On the other hand, Lu and coworkers [46] defined core-shell UiO-67@Ni-MOF composites based on an electrochemical sensing platform to detect glucose through a non-enzymatic process. The fabricated core-shell materials based on Ni-MOF (nickel Qiaoand et al. [45] presented the application of a conductive Ni-MOF, which is an on-noble-metal catalyst for proficient glucose electrooxidation in alkaline electrolytes. For glucose detection, this Ni-MOF demonstrated the LOD, stability, and sensitivity of 0.66 µM (S/N = 3), 30 days, and 21,744 µA mM −1 cm −2 , respectively, with a rapid response period of lower than 3 s. In addition, the conductive Ni-MOF exhibits a detection range from 0.001 to 8 mM. On the other hand, Lu and coworkers [46] defined core-shell UiO-67@Ni-MOF composites based on an electrochemical sensing platform to detect glucose through a non-enzymatic process. The fabricated core-shell materials based on Ni-MOF (nickel metal structure with 2,5-dihydroxyterephthalic acid as the ligand) and UiO-67 (Zr(IV) biphenyl dicarboxylate metal-organic framework) were fabricated by increasing the internal growth of Ni-MOF shell on a core of UiO-67 through polyvinylpyrrolidone (PVP) direction. By applying this sensing assay, UiO-67 with acceptable conductivity and a huge specific surface area was applied to accelerate the electron transport rate of the prepared nanocomposite. The synergistic effects of the electrocatalytic function of Ni-MOF and the conductivity of UiO-67 enabled glucose detection of the fabricated composite. Specification of electrochemical performance through the CV process revealed that the fabricated electrochemical sensor presented a good electrocatalytic function for glucose oxidation in alkaline environments. The surface morphology of UiO-67@Ni-MOF has been investigated by SEM. Figure 3A illustrates that the composite has a 3D structure with good dispersity. The TEM image of UiO-67@NiMOF reveals that the composite contains Ni-MOF nanosheets as the shell (light areas), and also an octahedral UiO-67 core (dark areas) on the UiO-67 surface ( Figure 3B). Moreover, energy-dispersive X-ray spectrometry (EDS) elemental mapping ( Figure 3C) reveals that elements including Ni, Zr, C, and O are present and distributed in homogeneous form. On the other hand, Figure 3D illustrates a graphical presentation of the related core-shell composite synthesis. The outcomes at optimum conditions indicate that the sensor contains a fast response (<5 s), LOD (0.98 µM), and an extensive linear range (5 µM to 3.9 mM). Additionally, this sensor has long-range stability, good repeatability (RSD = 1.9%), and reproducibility (RSD = 1.1%). Once the glucose LODs were applied in human serum models, this sensor was efficient in glucose recognition. nanosheets as the shell (light areas), and also an octahedral UiO-67 core (dark areas) on the UiO-67 surface ( Figure 3B). Moreover, energy-dispersive X-ray spectrometry (EDS) elemental mapping ( Figure 3C) reveals that elements including Ni, Zr, C, and O are present and distributed in homogeneous form. On the other hand, Figure 3D illustrates a graphical presentation of the related core-shell composite synthesis. The outcomes at optimum conditions indicate that the sensor contains a fast response (<5 s), LOD (0.98 μM), and an extensive linear range (5 μM to 3.9 mM). Additionally, this sensor has long-range stability, good repeatability (RSD = 1.9%), and reproducibility (RSD = 1.1%). Once the glucose LODs were applied in human serum models, this sensor was efficient in glucose recognition. Furthermore, Wei et al. [47] have synthesized Co3O4, CuO, and Cu2O nanorod arrays on Cu foam of a seaweed-like structure through stages of in situ growth including alkaline oxidation of CF, solvothermal reaction of Cu(OH)2 precursor, and annealing CoCu-MOF. Structure measurements displayed that the Cu(OH)2 nanorod arrays offered a stable template for the growth of CoCu-MOF nanosheets, inhibiting the aggregation of MOFs. After Furthermore, Wei et al. [47] have synthesized Co 3 O 4 , CuO, and Cu 2 O nanorod arrays on Cu foam of a seaweed-like structure through stages of in situ growth including alkaline oxidation of CF, solvothermal reaction of Cu(OH) 2 precursor, and annealing CoCu-MOF. Structure measurements displayed that the Cu(OH) 2 nanorod arrays offered a stable template for the growth of CoCu-MOF nanosheets, inhibiting the aggregation of MOFs. After annealing, CoCu oxides kept the morphology of nanorod arrays without any collapse and a porous structure was obtained. The prepared CoCu oxide/CF was directly used as a non-enzymatic glucose-sensing electrode without an additional fixed procedure. Through applying the fabricated electrode (CoCu-MOF/Cu 2 O/CFE), high sensitivity of 11.916 µA mM −1 cm −2 , a varied linear range of 0.001-1.07 mM, and detection limit of 0.72 µM have been obtained. The detection performance is related to the synergistic effect of metal oxides' high electrocatalytic function on binder-free electrodes and the appropriate catalytic sites of porous nanorod array morphology. In addition, acceptable feasibility and selectivity in human serum, first-rate stability, and reproducibility have also been achieved by applying CoCu oxides/CF electrodes, signifying that this may be promising for practical applications. Additionally, Abrori et al. [48] have provided FeBDC-derived Fe 3 O 4 MOF by the solvothermal process that was used for non-enzymatic electrochemical glucose recognition ( Figure 4A). Benzene-1,4-dicarboxylic acid (H 2 BDC) and FeCl 2 .4H 2 O have been applied in place of precursors to form FeBDC. The final MOF has micro-rod-like morphology and crystallinity. Figure 4B shows SEM images of (a) FeBDC and (b) FeBDCderived Fe 3 O 4 , which shows an amorphous nature of Fe 3 O 4 with a strongly defective surface. In addition, the thermogravimetry/differential thermal analysis (TG/DTA) curve of MOF FeBDC was presented in Figure 4C. CV and differential pulse voltammetry (DPV) of bare GCE, FeBDC/GCE, and Fe 3 O 4 /GCE were used in glucose determination as shown in Figure 4D In research reported by Jia et al. [25], a flower-like nanocomposite based on carbon and nitrogen and doped with NiO (CN-NiO) was fabricated via calcination of Ni-MOF and polyaniline (PANI) at a high temperature. This composite was applied in fabricating an enzyme-free sensing platform by modifying GCE. The outcomes presented that the synthesized nanocomposite has a wide linear range according to the analytical response of glucose of a concentration 5.0 × 10 -7 -3 × 10 -3 mol/L. The proposed assay has greater sensitivity and lower LOD of 1144 μA/mM.cm 2 and 5.0 × 10 -7 mol/L, respectively. Simultaneously, this electrode has high selectivity with no electrochemical signal interference with nifedipine, dopamine, ascorbic acid, and urea. Another example is the technique developed by Wang et al. [49] (Figure 5A), which is a hierarchical 3D MOF based on flowerlike nickel (II)-terephthalic acid (Ni(TPA)) fabricated by a straightforward solvothermal process. Afterward, single-walled carbon nanotubes (SWCNT) and the fabricated MOF were integrated by applying the ultrasonic process to enhance the electrochemical function and the chemical stability of the composite. To study the probable application of the fabricated agent, its application as a non-enzymatic electrochemical sensor for glucose determination was investigated. Moreover, the nanocomposite has a 2.5 times higher electrochemical response for glucose determination compared with single SWCNT and fabricated Ni(TPA). The SEM image of Ni(TPA) is depicted in Figure 5B; as reported, the av- In research reported by Jia et al. [25], a flower-like nanocomposite based on carbon and nitrogen and doped with NiO (CN-NiO) was fabricated via calcination of Ni-MOF and polyaniline (PANI) at a high temperature. This composite was applied in fabricating an enzyme-free sensing platform by modifying GCE. The outcomes presented that the synthesized nanocomposite has a wide linear range according to the analytical response of glucose of a concentration 5.0 × 10 -7 -3 × 10 -3 mol/L. The proposed assay has greater sensitivity and lower LOD of 1144 µA/mM.cm 2 and 5.0 × 10 -7 mol/L, respectively. Simultaneously, this electrode has high selectivity with no electrochemical signal interference with nifedipine, dopamine, ascorbic acid, and urea. Another example is the technique developed by Wang et al. [49] (Figure 5A), which is a hierarchical 3D MOF based on flower-like nickel (II)-terephthalic acid (Ni(TPA)) fabricated by a straightforward solvothermal process. Afterward, single-walled carbon nanotubes (SWCNT) and the fabricated MOF were integrated by applying the ultrasonic process to enhance the electrochemical function and the chem-ical stability of the composite. To study the probable application of the fabricated agent, its application as a non-enzymatic electrochemical sensor for glucose determination was investigated. Moreover, the nanocomposite has a 2.5 times higher electrochemical response for glucose determination compared with single SWCNT and fabricated Ni(TPA). The SEM image of Ni(TPA) is depicted in Figure 5B; as reported, the average thickness and the average distance among adjacent nanosheets have been evaluated to be about 25 nm and 50 nm, respectively. On the other hand, TEM images for the fabricated composite (Ni(TPA)-SWCNT) display that the microspheres are enclosed by SWCNT which have wire shapes ( Figure 5C), approving the successful construction of the Ni(TPA)-SWCNT nanocomposite. As found in characterization investigations, all diffraction peaks of Ni(TPA) are preserved, proposing the retaining of the Ni(TPA) crystalline phases after doping with the SWCNT for the fabrication of nanocomposites. Furthermore, a new peak at 2θ = 26 • is associated with the plane of the SWCNT, approving the existence of the carbon nanomaterial ( Figure 5D). FT-IR characterization of Ni(TPA) and its composite with SWCNT are also demonstrated in Figure 5E. Electrochemical behaviors of (a) GCE modified with SWCNT-CS/, (b) GCE modified with Ni(TPA)-CS, and (c) GCE modified with Ni(TPA)-SWCNT-CS, are confirmed in Figure 5F. For glucose detection, the Ni(TPA)-SWCNT-CS modified electrode showed great analytical features, such as broad linear range, low LOD, and rapid response of 20 µM to 4.4 mM, 4.6 µM, <5 s, respectively, in addition to high selectivity. The developed sensor showed an agreement with the automatic biochemical analyzer used for glucose detection in real serum models. A correlation coefficient (r) of 0.9940 (n = 20, p < 0.0001) and a deviation rate of 0-6.7% were detected, which indicates the precision and potential of the sensor.
Peng et al. provided a nanocomposite of AgNPs/MOF-74 (Ni (II) as metal ions and 2,5dioxido-1,4-benzenedicarboxylate as organic linkers) and applied it for glucose recognition through the electrochemical method. Current-time curve (I-t curve) and CV with threeelectrode systems have specified the electrochemical exclusivities of the GC electrodes immobilized with the MOF-74(Ni) and Ag NPs. To sum up, the AgNPs/MOF-74(Ni) composite was set by agitation and hydrothermal treatment, and glucose oxidation was effectively promoted. The electrochemical sensing of AgNPs/MOF-74(Ni) demonstrated an LOD, sensitivity, and a broad linear range of 4.7 µM, 1.29 mA mM −1 cm −2 , and 0.01~4 mM for glucose detection, respectively. Hence, the AgNPs/MOF-74(Ni) composite is sensible, stable, and reproducible, and has a high potential for glucose detection in biomedical applications [50]. Furthermore, Zhang et al. [51] reported an effective electrocatalyst agent by combining Ni 2 P NPs with a graphene film to prepare the Ni 2 P/G nanocomposite. The prepared composite showed a highly sensitive determination of glucose in an enzyme-free manner. By applying Ni-MOF-74 as a precursor, Ni 2 P/G presented massive exposure to active sites, even metal distribution, spatial systematic structure, and high electrocatalytic specificity toward glucose electrooxidation. In optimum conditions, a wide-range linear response from 5 µM to 1.4 mM was achieved with a 0.44 µM LOD. The sensitivities of Ni 2 P/G/GCE are 7234 µM, 1.29 mA mM −1 cm −2 . Moreover, through applying a Ni 2 P/G modified electrode, appropriate linearity (R 2 = 0.9897) has also been achieved in real human serum with glucose concentrations ranging from 1 mM to 8 mM. In brief, an effective electrocatalyst for non-enzymatic glucose sensors founded on MOF-derived composite has been stated. As the electrocatalytic reaction is set, Ni 2 P/G has the advantages of good electrochemical presentation towards glucose, and high specificity and selectivity for glucose determination in human serum and buffer solution. Furthermore, eco-friendly preparation and low cost have also enhanced the possibility of the application of this composite in actual models. In addition, Meng et al. [52] first applied a Co-based porous ZIF-67 as a glucose electrochemical sensor. A first-rate catalytic function against glucose oxidation was presented by the GCE modified with ZIF-67. Meanwhile, by applying a sequential deposition-reduction technique, an Ag@ZIF-67 nanocomposite was developed to modify the electrocatalytic electrode. The Ag@ZIF-67/GCE presented an enriched catalytic function against the oxidation of glucose. The electrocatalytic activity of Ag@ZIF-67 of different Ag loadings from 0% to 0.5% was presented and the sensitivity was improved by two times and a half. Here, the response period of the modified electrode decreased by more than two times. The Ag-0.5%@ZIF-67GCE displayed a good electrocatalytic presentation in a glucose concentration range of 2-1000 µM; hence, high sensitivity and low LOD of 379 µA. mM −1 cm −2 and 0.66 µM (S/N = 3), respectively, were achieved with good stability and selectivity. In research done by Li et al. [53], the hydrothermal construction of a Co-MOF nanosheet array on nickel foam from aqueous Co 2+ and terephthalic acid as an organic ligand has been testified. High activity of glucose oxidation electrocatalysis has resulted from the Co-MOF array on Ni foam (Co-MOF/NF) in alkaline media. In the Co-MOF/NF, linear rang speedy amperometric response, low LOD, and high sensitivity of 0.001-3 mM, < 5 s, 1.3 nM (signal/noise = 3), and 10,886 µA mM −1 cm −2 , respectively, have been achieved. As this study demonstrated that the material has high reproducibility and long-time stability, it may be applied for glucose recognition in fruit juice and human blood serum. SWCNT which have wire shapes ( Figure 5C), approving the successful construction of the Ni(TPA)-SWCNT nanocomposite. As found in characterization investigations, all diffraction peaks of Ni(TPA) are preserved, proposing the retaining of the Ni(TPA) crystalline phases after doping with the SWCNT for the fabrication of nanocomposites. Furthermore, a new peak at 2θ = 26° is associated with the plane of the SWCNT, approving the existence of the carbon nanomaterial ( Figure 5D). FT-IR characterization of Ni(TPA) and its composite with SWCNT are also demonstrated in Figure 5E. Electrochemical behaviors of (a) GCE modified with SWCNT-CS/, (b) GCE modified with Ni(TPA)-CS, and (c) GCE modified with Ni(TPA)-SWCNT-CS, are confirmed in Figure 5F. For glucose detection, the Ni(TPA)-SWCNT-CS modified electrode showed great analytical features, such as broad linear range, low LOD, and rapid response of 20 μM to 4.4 mM, 4.6 μM, <5s, respectively, in addition to high selectivity. The developed sensor showed an agreement with the automatic biochemical analyzer used for glucose detection in real serum models. A correlation coefficient (r) of 0.9940 (n = 20, p < 0.0001) and a deviation rate of 0-6.7% were detected, which indicates the precision and potential of the sensor.

Highly Sensitive Electrochemical Sensing and Biosensing Assays for H 2 O 2 Determination
On the other hand, the electrochemical mechanism of H 2 O 2 determination for developing enzyme-free electrochemical determination of H 2 O 2 is based on the electrochemical oxidation of H 2 O 2 to H 2 O through applying the electroactive agents related to the syn-thesized. Table 2 demonstrates various electrochemical-based detecting platforms for the highly sensitive determination of H 2 O 2 and some of the electrochemical research works have been described here. Huang et al. [61] developed a sensitive electrochemical sensing platform based on an active dual nanozyme amplified process by applying conductive MOF (C-MOF) nanosheets (NSs). These composites were fabricated from Au NPs and utilized in H 2 O 2 recognition, a biomarker for cancer in living cells. Due to the high catalytic and electrical functions of Cu-HHTP-NSs and AuNPs, the provided nanocomposite immobilized electrode demonstrated well-detecting presentation to H 2 O 2 with a low LOD and sensitivity of 5.6 nM (3σ rules) and 188.1 µA cm −2 mM −1 , respectively. Moreover, the non-enzymatic biosensing platform was employed in H 2 O 2 in a real-time manner, which has been released from dissimilar human colon cells to distinguish colon cancer cells from normal colon epithelial cells. This revealed its great role in the prompt diagnosis and management of different types of cancer. In another work by Wang et al. [62], a nanozyme sensor was developed based on an electrochemical sensing approach to recognize H 2 O 2 concentration in living cells. By exploiting the high specific surface area of porous ZIF-67 MOF and the electrocatalytic function of Au@Pt core-shell bimetallic nanoflower structure, the non-enzyme sensor was assembled. The outcome presented that the sensor had a wide-ranging linear relationship of 0.8 µM-3 mM H 2 O 2 , while the LOD, sensitivity, and correlation coefficient were 86 nM, 24.14 µA mM −1 cm −2 , and 0.9936, respectively. Furthermore, Cheng et al. [63] fabricated a unique 3D flower-like Cu-MOF (benzene-1,3,5-tricarboxylate applied as a ligand) assembled with MXene to synthesize an electro-chemical H 2 O 2 sensor ( Figure 6A). The catalytic function of Cu-MOF/MXene/GCE resulted in the detection due to the electrical conductivity of MXene, the nature of Cu, and the framework exclusivities of MOFs. As shown in Figure 6B, Cu-MOF is a three-dimensional flower-like structure composed of ultra-thin nanosheets, and Figure 6C depicts the EDS elemental mapping of O, N, C, and Cu of the synthesized MOF. Moreover, the electrochemical examination is performed as shown in Figure 6D, in which the CVs related to the GCE modified with MXene (a and b), GCE modified with Cu-MOF (c and d), and GCE modified with Cu-MOF and MXene (e and f) are shown. Moreover, Figure 6E demonstrates the electrochemical responses of chronoamperometric related to the GCE. Figure 6F is also related to the CV responses of (F) five independent Cu-MOF/MXene/GCE. The GCE modified with Cu-MOF and MXene presented a detection range of 1 µM to 6.12 mM using chronoamperometry with an estimated LOD of 0.35 µM at a sensing potential of −0.35 V. For now, the electrochemical sensor could be applied to recognize H 2 O 2 in serum and milk models with pleasing outcomes. The easy operation, quick recognition, and sensitivity of the provided sensor have exhibited a noteworthy achievement for H 2 O 2 monitoring and real-time analysis in biological models and foodstuffs. 6F is also related to the CV responses of (F) five independent Cu-MOF/MXene/GCE. The GCE modified with Cu-MOF and MXene presented a detection range of 1 μM to 6.12 mM using chronoamperometry with an estimated LOD of 0.35 μM at a sensing potential of -0.35 V. For now, the electrochemical sensor could be applied to recognize H2O2 in serum and milk models with pleasing outcomes. The easy operation, quick recognition, and sensitivity of the provided sensor have exhibited a noteworthy achievement for H2O2 monitoring and real-time analysis in biological models and foodstuffs. In another work, an innovative method for Sn-based MOF (Sn-MOF) was assembled by the solvothermal process and integrated with CNT by sonochemical tools to introduce the Sn-MOF@CNT composite that was applied to H2O2 detection. The electrochemical detection of Sn-MOF@CNT demonstrated an LOD and a linear range of ~4.7 × 10 − 3 μM and 0.2 μM to 2.5 mM, respectively. This study has explored a new strategy for the deposition of CNT over Sn-MOF via a simple sonochemical methodology for successful electrochemical detection of H2O2, an approach that can be imitated for other applications [64].
Sun et al. [65] investigated the morphology effects and electrocatalytic function of ZIF-67 (Co zeolitic imidazolate framework-67) as a supporting substance ( Figure 7A). Three kinds of ZIF-67 MOF were prepared and the morphological structures were controlled by altering the solvent by applying a polar solvent to the crystal growth and nucleation. Pure H2O (H-ZIF-67) and a mixed solution of DMF and H2O (D-ZIF-67) formed In another work, an innovative method for Sn-based MOF (Sn-MOF) was assembled by the solvothermal process and integrated with CNT by sonochemical tools to introduce the Sn-MOF@CNT composite that was applied to H 2 O 2 detection. The electrochemical detection of Sn-MOF@CNT demonstrated an LOD and a linear range of~4.7 × 10 −3 µM and 0.2 µM to 2.5 mM, respectively. This study has explored a new strategy for the deposition of CNT over Sn-MOF via a simple sonochemical methodology for successful electrochemical detection of H2O2, an approach that can be imitated for other applications [64].
Sun et al. [65] investigated the morphology effects and electrocatalytic function of ZIF-67 (Co zeolitic imidazolate framework-67) as a supporting substance ( Figure 7A). Three kinds of ZIF-67 MOF were prepared and the morphological structures were controlled by altering the solvent by applying a polar solvent to the crystal growth and nucleation. Pure  Figure 7B-D, respectively. Additionally, Figure 7E represents the XRD patterns which confirm the crystal phase of the patterns of the above-mentioned fabricated compounds. The electrochemical behaviors of the four electrodes and amperometric signals of GCE-modified Ag/H-ZIF-67 to the addition of (a) low and (b) high H 2 O 2 concentration are illustrated in Figure 7F,G, respectively. The electrochemical H 2 O 2 sensor presented a low detection limit of 1.1 µM, sensitivity amounts of 337.7 and 421.4 µA mM −1 cm −2 , and two linear ranges of 7 mM-67 mM and 5 µM-7 mM. Furthermore, this sensor has superb stability, reproducibility, and selectivity. In addition, the sensor has been applied for real-time recognition of H 2 O 2 from HepG2 human liver cancer cells. The research process provided a method to track the sensing potential of electrochemical sensors by changing the crystalline morphologies of supporting materials.  Figure 7E represents the XRD patterns which confirm the crystal phase of the patterns of the above-mentioned fabricated compounds. The electrochemical behaviors of the four electrodes and amperometric signals of GCE-modified Ag/H-ZIF-67 to the addition of (a) low and (b) high H2O2 concentration are illustrated in Figure 7F,G, respectively. The electrochemical H2O2 sensor presented a low detection limit of 1.1 μM, sensitivity amounts of 337.7 and 421.4 μA mM −1 cm −2 , and two linear ranges of 7 mM-67 mM and 5 μM-7 mM. Furthermore, this sensor has superb stability, reproducibility, and selectivity. In addition, the sensor has been applied for real-time recognition of H2O2 from HepG2 human liver cancer cells. The research process provided a method to track the sensing potential of electrochemical sensors by changing the crystalline morphologies of supporting materials. Wang et al. [66] synthesized 2D MOF nanosheets that combined with MWCNT films and immobilized them on electrodes as an electrochemical component for H2O2 detection. Two-dimensional Cu-TCPP/MWCNTs/GCE showed 0.70 μM LOD (S/N = 3), a sensitivity of 157 μA cm −2 mM −1 , a short response time of fewer than 3 s, and a linear range from 0.001 to 8.159 mM. The occurrence of MWCNTs with high electrical conductivity has enhanced the sensitivity of composite films in comparison with the original 2D MOF nanosheets. Figure 8A represents the graphic steps of the 2D Cu-TCPP (copper-tetrakis (4-carboxyphenyl) porphyrin)/MWCNTs preparation process. Electrochemical behavior of the bare GCE, GC modified with MWCNTs, GC modified with two-dimensional Cu-TCPP, GC Wang et al. [66] synthesized 2D MOF nanosheets that combined with MWCNT films and immobilized them on electrodes as an electrochemical component for H 2 O 2 detection. Two-dimensional Cu-TCPP/MWCNTs/GCE showed 0.70 µM LOD (S/N = 3), a sensitivity of 157 µA cm −2 mM −1 , a short response time of fewer than 3 s, and a linear range from 0.001 to 8.159 mM. The occurrence of MWCNTs with high electrical conductivity has enhanced the sensitivity of composite films in comparison with the original 2D MOF nanosheets. Figure 8A represents the graphic steps of the 2D Cu-TCPP (copper-tetrakis (4-carboxyphenyl) porphyrin)/MWCNTs preparation process. Electrochemical behavior of the bare GCE, GC modified with MWCNTs, GC modified with two-dimensional Cu-TCPP, GC modified with two-dimensional Cu-TCPP/MWCNTs, and GC modified with three-dimensional Cu-TCPP/MWCNTs electrodes are shown in Figure 8B. Moreover, Figure 8C shows the amperometric signals of the bare glassy carbon, GC-modified electrode with MWCNTs, GC-modified electrode with two-dimensional Cu-TCPP, twodimensional Cu-TCPP/MWCNTs/GC, and GC-modified electrode with three-dimensional Cu-TCPP/MWCNTs. Moreover, impedance spectra of the bare glassy carbon, GC-modified MWCNTs, 2D Cu-TCPP, and 2D Cu-TCPP/MWCNTs electrodes have been indicated in Figure 8D. MWCNTs, GC-modified electrode with two-dimensional Cu-TCPP, two-dimensional Cu-TCPP/MWCNTs/GC, and GC-modified electrode with three-dimensional Cu-TCPP/MWCNTs. Moreover, impedance spectra of the bare glassy carbon, GC-modified MWCNTs, 2D Cu-TCPP, and 2D Cu-TCPP/MWCNTs electrodes have been indicated in Figure 8D. The sensitive, selective straightforward, and stable H2O2 sensors are suitable for H2O2 detection in actual models; beer and serum are examples. In another work by Menon et al. [12], a copper-MOF fabricated via solvothermal conditions was presented to show a basic peroxidase-like function that has been electrochemically and spectro-photometrically developed. To sense glucose, the peroxidase mimics could be combined with the enzymatic oxidation of glucose. The recognition of glucose and H2O2 through applying Cu-MOF was highly selective to the common interfering species. The amperometric response presented the efficacy of Cu-MOF modified electrode towards H2O2 with sensitivity, linear range, and an LOD of 263 μA mM −1 cm −2 , 25 μM -30000 μM, and 25 μM (S/N = 3), respectively, at an applied voltage of 0.50 V.

Conclusions and Future Outlooks
This review paper has presented a summary of the electrochemical-based investigations of glucose and H2O2 by applying MOF-based compounds. The MOF-based nano- In another work by Menon et al. [12], a copper-MOF fabricated via solvothermal conditions was presented to show a basic peroxidase-like function that has been electrochemically and spectro-photometrically developed. To sense glucose, the peroxidase mimics could be combined with the enzymatic oxidation of glucose. The recognition of glucose and H 2 O 2 through applying Cu-MOF was highly selective to the common interfering species. The amperometric response presented the efficacy of Cu-MOF modified electrode towards H 2 O 2 with sensitivity, linear range, and an LOD of 263 µA mM −1 cm −2 , 25 µM −30,000 µM, and 25 µM (S/N = 3), respectively, at an applied voltage of 0.50 V.

Conclusions and Future Outlooks
This review paper has presented a summary of the electrochemical-based investigations of glucose and H 2 O 2 by applying MOF-based compounds. The MOF-based nanomaterials are of great importance and are experiencing much demand for developing glucose and H 2 O 2 sensors due to their remarkable fabrication technologies, widespread and comprehensive study, and high sensitivity, as well as application of innovative electrode materials. However, attaining higher selectivity, fast response time, sensitivity, miniaturization, stability, reliable accuracy and precision, and automatic systems have always been significant challenges in designing a new sensing platform. In this regard, only a few sensing platforms apply to in vivo determinations and there are still requirements for developing methods for the detection of glucose and H 2 O 2 in biological applications. We have comprehensively reviewed the recent trends in the design of glucose and H 2 O 2 sensors by using MOF-based nanomaterials. These compounds are porous organic-inorganic hybrid materials with strong adsorption capacity, excellent catalytic ability, large specific surface area, and efficient loading capability. Based on this, to detect glucose and H 2 O 2 , MOF-based electrochemical approaches have been provided as sensing tools with exceptional selectivity and responsiveness using progressive nanostructures and smaller devices. Additional progress in these methods is probable through integrating various approaches to overcome the limitations. The upcoming research work aims to emphasize progressing low-complexity techniques for amateurs. As demonstrated, a wide range of enzyme-and non-enzyme-based biosensors can be effectively established for the sensitive determination of both glucose and H 2 O 2 . In addition, enzyme-free-based biosensors have been verified to be the most promising ones. As a prospect, the application of immunosensors, which utilize antigens or antibodies as specific biosensors for the recognition of glucose and H 2 O 2 , is promising. This technique is more specific than the enzyme-based biosensing one. Moreover, applying novel MOFs with innovative synthesized techniques unlocks new potentials in sensing and biosensing approaches.

Data Availability Statement:
The data presented in this study are available on request from the corresponding author.