Progress in Electrochemical Sensing of Ascorbic Acid

Yanyu Zhong; Zhengyun Wang; Hongfang Liu

doi:10.7536/PC220723

Progress in Chemistry ›› 2023, Vol. 35 ›› Issue (2) : 219-232 DOI: 10.7536/PC220723

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Progress in Electrochemical Sensing of Ascorbic Acid

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Abstract

Ascorbic acid (AA), as a necessary biological small molecular substance to maintain the normal function of human body, directly and indirectly participates in many key biological reaction processes of human body. Electrochemical detection of AA has been a hot spot of sensing research in recent years due to the advantages such as fast response, high sensitivity and simple operation. In this review, the working principles of different sensors of AA are systematically and comprehensively introduced, and the recent research progress of electrochemical sensing of AA is reviewed. By comparing different materials based AA sensors performances, the advantages and defects of corresponding materials are analyzed and summarized by combining with the materials properties. Lastly, the outlook of development direction and trend of AA electrochemical sensing is given.

Contents

1 Introduction

2 Principles of electrochemical detection of ascorbic acid

3 Enzymatic sensors

4 Non-enzymatic sensors

4.1 Metal-based sensor

4.2 Conductive polymer-based sensor

4.3 Carbon material-based sensor

5 Conclusion and outlook

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Keywords

ascorbic acid / electrochemical sensor / enzymatic / nonenzymatic

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Yanyu Zhong, Zhengyun Wang, Hongfang Liu. Progress in Electrochemical Sensing of Ascorbic Acid. Progress in Chemistry, 2023, 35(2): 219-232 DOI:10.7536/PC220723

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1 Introduction

ascorbic acid (AA), also known as 2,3,5,6-tetrahydroxy-2-hexen-4-olide or vitamin C, plays an important role in maintaining normal physiological functions of the human body. As shown in Figure 1, the structure of AA has two dissociable protons of hexamonic acid, so AA generally exists in the form of ascorbate anion under normal physiological conditions, showing strong oxidation resistance and being easily oxidized to dehydroascorbic acid. Studies have shown that high concentrations of ascorbic acid anions in human nerve cells are involved in various physiological and pathological processes. For example, AA can act as a highly effective neuroprotective agent to scavenge intracellularly generated free radicals during oxidative stress caused by ischemic stroke, auditory dysfunction, olfactory dysfunction, etc^[1]^[2]^[3]. On the other hand, AA can also indirectly regulate neural function through neurotransmitters such as glutamate, choline, dopamine and aminobutyric acid^[4]. In addition to nerve cells, the content of AA in serum is also an important factor affecting human health^[5]. The standard reference range of AA in human serum is 0.28 ~ 1.28 mg/dL (1.6 ~ 7.3 μmol/L). When the concentration of AA in serum is lower than the standard value, it will lead to physical dysfunction and may cause a series of diseases, such as rheumatoid arthritis, scurvy, Parkinson's disease, Alzheimer's disease, cardiovascular disease, and even cancer. Excessive intake of AA can cause oxalic acid and uric acid stones, diarrhea, skin rash and other diseases and ^[6][7]. On the other hand, in the fields of cosmetics, pharmaceutical preparations and food industry, the content of AA should also be strictly controlled^[8⇓~10]. Based on this, the realization of highly sensitive detection of AA in human body and industrial products is the key issue in the field of modern advanced sensing, and is also the current research focus.

At present, the detection methods of AA mainly include Electrochemical analysis, Spectral analysis, Titration and Chromatography^{[11⇓⇓~14]}. Among them, titration and chromatography are greatly limited in complex practical applications because of their complex operation and time-consuming detection. Although chromatography is widely used in the actual detection of AA, it also has the disadvantages of time-consuming and expensive equipment. Electrochemical analysis has the characteristics of fast response, low detection limit, simple operation and high sensitivity, which is very suitable for wearable, on-site analysis and other application scenarios, and has outstanding advantages in AA sensing. Accord to that method, a three-electrode system is established, and the relationship between an electrochemical signal and the concentration of a t substance is established according to the change of electrochemical properties (such as resistance, current, potential and capacitance) of the t substance in the system, so that the accurate detection of the test substance is realized. In this paper, the main principle of electrochemical detection of AA is described in detail, and the electrode materials used in electrochemical detection of AA and their research progress are systematically and comprehensively reviewed. The main advantages and disadvantages of various materials are summarized, and the future development direction of electrochemical detection for AA is prospected.

2 Main principles of electrochemical detection of AA

The electrochemical detection mechanism of AA is usually amperometric. Due to the different working electrodes, AA electrochemical detection sensors can be divided into enzymatic and non-enzymatic working electrodes. These two types of working electrodes oxidize AA and output the response of electrode active materials to AA in the form of current signals. AA loses two electrons and releases two protons to form dehydroascorbic acid during oxidation, and dehydroascorbic acid opens the lactone ring to produce 2,3-diketoacetic acid, which is not electrochemically active.

The process of electrochemical sensor detecting AA is shown in Fig. 2. For the enzyme-based electrochemical sensor, AA is first captured by ascorbate oxidase through its selective adsorption, forming an AA-enzyme complex; Then AA reacts with oxygen (dissolved oxygen) under the catalysis of enzyme, and AA loses two electrons and releases two protons to form dehydroascorbic acid. Finally, the enzyme-AA complex releases and restores dehydroascorbic acid to active ascorbate oxidase for the next cycle. The redox signal generated during this cycle can be converted into an electrical signal through the electrode connected to the enzyme, thus realizing the detection of AA. Therefore, the properties of the enzyme load and the connection form between the enzyme and the carrier will affect the properties of the enzyme-based electrochemical sensor.

For enzyme-free electrochemical sensors, there are differences in the mechanism of AA oxidation reaction catalyzed by electrode materials during the sensing process. Firstly, the electrode material is "activated" by the electric field, and the catalytic material on the surface of the working electrode undergoes an oxidation-reduction reaction under the electric field to form an intermediate with certain oxidizability; Subsequently, AA is adsorbed to the active site of the catalytic active material and is rapidly oxidized by the active material to generate dehydroascorbic acid, while the catalytic material is reduced to the initial state; Finally, the dehydroascorbic acid is released from the catalytic active material due to diffusion, and the catalytic material in the initial state enters the next cycle under the action of constant voltage. Therefore, the electrochemical properties of AA's enzyme-free sensing material itself will significantly affect its sensing performance.

3 Electrode Materials for AA Electrochemical Sensor

3.1 Enzymatic AA electrochemical sensor

Ascorbate oxidase is a protein that is very sensitive to the external environment. Overheating or inappropriate pH environment will lead to enzyme inactivation. According to the detection principle of enzymatic electrochemical sensor, the reduction of oxygen is related to the concentration of AA, and the reduction of oxygen concentration will increase with the increase of AA concentration. Therefore, it is a common detection method to obtain the concentration of AA by detecting the change of oxygen concentration. Based on this, early researchers mixed ascorbic acid oxidase with porous carbon materials, polymers and nano-metal materials and immobilized them on oxygen electrodes (such as Clark oxygen electrodes) that can measure the dissolved oxygen content in solution, and successfully realized the detection of AA concentration^{[15⇓⇓~18]}. In 2020, Sempionatto et al. Developed a wearable sensor based on ascorbate oxidase, which realized the tracking of human sweat AA for the first time, as shown in Figure 3^[19]. They immobilized ascorbate oxidase on a flexible printable tattoo electrode and monitored changes in AA concentration levels by detecting changes in oxygen co-substrate reduction current. The tattooed sensing electrode is based on polyurethane and incorporates a local iontophoretic sweat stimulation system and an amperometric cathode detector that detects oxygen consumption. The electrode array of the device consists of a sweat-stimulated iontophoresis electrode, an Ag/AgCl reference electrode and a carbon counter electrode, and the sensing circuit wire is printed with stretchable silver ink. The test results of the sensor show that the device has the characteristics of bending and folding, comfortable wearing, good selectivity and good biocompatibility, and can be used for nutritional status assessment and nutritional intake tracking. Although the introduction of oxygen electrode can realize the detection of AA in experiments, such sensors based on the correlation between oxygen and ascorbic acid can only indirectly determine the concentration of AA by detecting the consumption of oxygen, so there are many problems.For example, the adsorption of oxygen on the material, the gas flow rate of the detection environment, the adsorption reaction of oxygen on the electrolyte, and the saturation of dissolved oxygen in the electrolyte will affect the electrochemical performance of the sensor, such as sensitivity, response time, detection limit and detection accuracy.

The study shows that ascorbate oxidase also has direct electrochemical behavior after the application of voltage^[20]. In 1998, Santucci et al. Studied the direct electrochemical behavior of ascorbate oxidase under aerobic and anaerobic conditions^[21]. The results showed that the electrocatalytic activity of ascorbate oxidase was only affected by type Ⅰ copper under anoxic conditions, and type Ⅱ and type Ⅲ copper showed electrocatalytic activity only under sufficient oxygen, in which type Ⅰ copper was in a distorted tetrahedral coordination environment. Type Ⅱ copper is in the normal coordination state, showing a nearly square-pyramidal configuration; Type III copper contains pairs of diamagnetically coupled dinuclear coppercenters whose coordinating atoms consist mainly of the imidazole nitrogen of histidine. The location of different types of Cu in ascorbate oxidase and the manner of enzyme immobilization are shown in fig. 4^[21].

Based on the study of electrochemical behavior of ascorbic acid oxidase, researchers use the electrochemical behavior of ascorbic acid oxidase to determine AA, which solves the problems of insufficient dissolved oxygen content and the detection results easily affected by the external environment. In 2014, based on the direct electronic reaction between enzyme and electrode, Barberis and others innovatively combined enzyme-loaded sensors and enzyme-free sensors to form a sensor-biosensor system, and assembled it with a dual-channel telemetry device to simultaneously detect the AA content and antioxidant capacity of fruit juice^[23]. The detection voltage of the device is 0. 5 V, the linear detection range is 0. 26 ~ 20 μmol/L, and the data acquisition time is less than 2 min. Its most important feature is that it can distinguish the contribution value of AA and phenolic substances in the detected substance to the antioxidant capacity. In 2021, Javey et al. Developed a wearable sensor that can selectively measure AA concentration in sweat, as shown in Fig. 5^[32]. The sensor uses polyethylene terephthalate (PET) as a flexible substrate to fully and closely contact with the skin, and uses Au nano-dendrite, conductive polymer doped with LiClO₄, and enzyme immobilized film layer for simple surface modification to enhance the sensitivity, stability, and selectivity of AA detection, thereby achieving selective detection of a wider range of AA concentrations. The experimental results show that the sensor successfully monitors the temporal changes of AA concentration levels in sweat and urine, and can be used to assess the nutritional health status of hospitalized patients and the general population. In addition, poly (3,4-ethylenedioxythiophene)/multi-walled carbon nanotube composite film, poly (3,4-ethylenedioxythiophene)/single-walled carbon nanotube/nafion film, nano-titanium dioxide/indium tin oxide film, poly (3, 4-ethylenedi oxythiphene) -lauroyl sarcosine film and other composite materials have also been found to be good carriers for ascorbate oxidase to promote the electron transport reaction of the enzyme^{[24⇓⇓⇓⇓⇓⇓~31]}. The sensors prepared based on the above materials can realize the selective detection of AA, the detection signal is not interfered by other small biological molecules, and the lowest detection limit can reach the micromolar level. However, there is no relevant article to confirm that there is a direct electron transfer process between ascorbate oxidase and the carrier, so the specific catalytic mechanism of the enzyme in anaerobic medium at a more positive potential needs further study.

In a word, enzyme-based sensors are generally composed of enzyme-loaded matrix and electrode materials, which have many advantages, such as strong selectivity, high sensitivity, good biocompatibility and so on. Although the complex structure of enzyme protein can eliminate the interference of most small biological molecules, there are some problems in the preparation and application of enzyme sensors. On the one hand, the immobilization of enzyme on the substrate is a tedious work. Whether the immobilization is based on the reaction of enzyme with organic groups or the action of electrostatic attraction, the reaction conditions must be strictly controlled during the experiment to ensure the activity of enzyme. On the other hand, the enzyme is extremely sensitive to pH and temperature, so the catalytic process has extremely strict requirements on the environmental conditions, and the inappropriate test environment can easily cause irreversible damage to the enzyme, thereby leading to the degradation or failure of the sensor. The practical application of enzyme-based biosensors is seriously restricted by the properties of enzymes, such as easy inactivation and difficult preservation.

In order to solve the problems caused by the properties of enzymes, researchers have developed a series of other materials as alternatives to enzymes, such as precious metal nanoparticles, conductive polymers and other materials. In the following, the research progress of electrode materials for enzyme-free sensors is reviewed, and the advantages and disadvantages of various materials are summarized.

3.2 Non-enzymatic AA electrochemical sensor

Many functional materials with good conductivity have been proved to be used as working electrodes of enzyme-free AA sensors. Based on the different types of materials for AA sensors, enzyme-free materials can be divided into three categories: metal-based materials, conductive polymer materials and carbon-based materials.

3.2.1 Metal based material

Noble metals such as Pt, Au and Pd have been proved to have the performance of electrocatalytic oxidation of AA. Kim et al. Used Pt as the working electrode and applied a voltage of 0. 6 V compared with the Ag/AgCl reference electrode to detect the concentration of AA by voltammetry^[33]. Kim et al. First used the ion exclusion method to extract and purify AA, and then monitored the AA concentration by electrochemical-UV detection and 2,6-dichloroindophenol titration. The experimental results show that the electrochemical detection has better sensitivity and selectivity compared with UV detection and titration. Based on this principle, Wawrzyniak et al. Successfully designed a detection system that can directly detect AA content in apple juice^[34]. The system uses Pt sheet as the working electrode, Pt wire as the auxiliary electrode, Ag/AgCl electrode as the reference electrode, and uses voltammetry to achieve quantitative detection. The difference between the measured results and the results of titration is very small, about 0.59 mg/100 cm³ (the concentration of ascorbic acid is 46.92 mg/100 cm³, and the standard deviation is 0.29), which proves the feasibility of the system for the measurement of AA content in practice. However, the bare noble metal electrode has some unavoidable defects. On the one hand, the irreversible oxidation behavior of AA on the bare electrode will lead to electrode contamination. On the other hand, the low specific surface area of the bare noble metal electrode can not provide satisfactory sensitivity. To solve these problems, it is a good choice to modify the surface of the working electrode with suitable electrochemically active materials. Unlike bulky bare noble metals, noble metal nanoparticles have unique catalytic properties, electronic conduction properties, optical properties, and magnetic properties. The combination of nanoscale particle size and unique physicochemical properties has made noble metal nanoparticles widely used in biosensors. The noble metal nanoparticle modified electrode surface can provide a more electrochemically active surface and increase the electron transfer rate of the electrode, so that the modified electrode has a larger electrochemical response current and higher sensitivity, and the applied potential required for the electrochemical reaction is reduced. In 2015, Oko et al. Prepared a series of PtAu nanoparticles with different metal ratios by impact laser ablation, and the PtAu alloy nanoparticles were used to detect AA^[35]. There are a lot of AA oxidation sites and adsorption sites on the surface of nano-alloy particles. The experimental results show that nano-Au and nano-Pt in the alloy participate in the process of AA oxidation.The peak current of the electrode modified by alloy nanoparticles was much higher than that of the unmodified electrode, and the peak current of the alloy nanoparticles was about 4 times higher than that of the pure Au nanoparticles. Modifying noble metals on materials with special morphologies is also a good strategy to improve the electrochemical performance of materials. In 2019, Zhao et al. Combined gold nanorods, graphene oxide and multi-walled carbon nanotubes to prepare a modified glassy carbon electrode with high sensitivity^[36]. Among them, graphene oxide can prevent the aggregation of multi-walled carbon nanotubes, so that the modified electrode has a larger specific surface area. The positively charged gold nanorods can reduce the overpotential of the electrochemical reaction and increase the peak current of AA oxidation, which makes the sensor show good electrochemical properties at low potentials. The results showed that the sensor could work at a low voltage of 0. 036 V (vs Ag/AgCl), with a detection limit of 0. 85 nmol/L and a wide linear range (1 nmol/L ~ 0.5 μmol/L, 1 μmol/L ~ 8 mmol/L), and was successfully applied to the quantitative detection of AA in spiked serum. In 2020, Luo et al. Successfully deposited Au and Pd mixed nanoparticles on chitosan and N-doped graphene modified glassy carbon electrode by a simple electrodeposition method, and the prepared electrode had good electrocatalytic ability^[37]. The increase of current response and the decrease of oxidation overpotential after electrode modification prove that the deposition of mixed noble metal nanoparticles can enhance the electrocatalytic ability of the material. The results show that the sensor can simultaneously detect three substances closely related to vitamin C injection, AA, sulfite and oxalic acid, with a detection limit of 0. 97 μmol/L for AA and a detection range of 1. 5-500 μmol/L, and can be used for the overall quality control of clinical drugs. In addition, Arroquia et al. Reported a novel sensor based on screen-printed carbon electrode covalently linked with self-assembled gold-modified polydopamine nanospheres (Au-PDN),The modified electrode showed electrochemical response to AA, dopamine, uric acid and tryptophan, and could detect the four substances simultaneously under weak acidic (pH = 6) conditions. The detection limit for AA was as low as 0.2 nmol/L, and the linear range was 1 ~ 160 μmol/L^[38]. Bettazzi et al. Deposited reduced graphene oxide nanosheets modified by gold nanoparticles on a screen-printed carbon electrode, and combined gold nanoparticles (AuNPs), graphene (RGO), and screen-printed carbon electrode (SPCE) to prepare a nanocomposite modified electrode (AuNPs/RGO/SPCEs), which showed excellent sensitivity with a detection limit for AA as low as 0.5 μmol/L^[39]. In 2021, Yazan et al. Deposited gold nanoparticles on L-methionine modified pencil graphite electrode by electrodeposition, and prepared a sensor for simultaneous detection of AA, acetaminophen, chlorpheniramine maleate and caffeine^[40]. Compared with the bare pencil graphite electrode, the modified electrode can improve the electrocatalytic activity of AA oxidation, the anodic peak current is significantly increased to 30. 9%, and the modified electrode has a wide linear detection range (10 ~ 2 000 μmol/L).The method has been successfully applied to the simultaneous quantification of AA, acetaminophen, chlorpheniramine maleate, and caffeine in drug doses and serum samples.

Although the electrochemical properties of the sensor can be improved by using nano-noble metal to modify the electrode, in general, the defects of using noble metal materials as the sensor electrode are still obvious, such as the high cost of noble metal materials and the general selectivity. These defects have hindered a large number of applications of noble metal materials in the sensing field. Non-precious metal materials (Cu, Co, Ni, MOFs, etc.) Have always been the most popular electrochemical catalytic materials for researchers. Studies have shown that transition metals, transition metal complexes, rare earth metal materials and so on can be applied to the electrochemical sensing of AA.

Copper is a naturally abundant low-cost metal that has been shown to have excellent electrocatalytic properties for AA. Rohani et al. Prepared a zeolite with Cu²⁺ adsorbed on its surface by adding a small amount of zeolite into copper nitrate solution and stirring for 24 H. Then, graphite powder and zeolite A loaded with Cu²⁺ were ground and suspended in a mixture of tetrahydrofuran and PVC. Finally, the clean platinum electrode was modified by the suspension^[41]. Aft that solvent is evaporated, the modify platinum electrode modified with the loaded Cu²⁺ zeolite is obtained. The results showed that the electrode combined the excellent pore selectivity, good particle exchange ability of zeolite and the catalytic oxidation property of Cu²⁺, which made it have good activity and selectivity for the electrochemical catalytic oxidation of AA, the detection limit was as low as 0. 276 μmol/L, and the linear detection range was 30 ~ 600 μmol/L, which could be applied to the detection of AA in effervescent tablets, chewable tablets and other samples. Selvaraju et al. Deposited Cu on the graphene-modified ITO electrode based on the electrochemical deposition method, and successfully prepared the Cu-modified GC/ITO electrode for the detection of AA in vitamin C tablets and human body fluids (serum and urine)^[42]. In real electrochemical measurements, the oxidation peak current increased linearly with increasing AA concentration from 1 to 40 μmol/L. However, the disadvantage is that the electrode also has electrochemical response to uric acid and homovanillic acid at a specific voltage, and lacks certain selectivity. Raveendran et al. Obtained a sensor for detecting AA concentration in vitamin C tablets and urine by modifying screen-printed electrode (SPE) with Cu(OH)₂ nanorods^[43]. The detection principle is that Cu(OH)₂ is reduced to Cu⁺ by AA on the surface of the electrode, and then Cu⁺ is electrochemically oxidized to Cu²⁺ with a peak current at the potential of − 0.1 V. The detection potential was much lower than that required for direct electrochemical redox of AA. The sensor showed good linearity (0. 0125 ~ 10 mmol/L), sensitivity (268μA·mM·cm^-2) and selectivity for the detection of AA in PBS solution, and could accurately detect the concentration of AA in the mixed solution of AA, urea, glucose, uric acid, dopamine and some metal ions. Kurt Urhan et al. Proposed a new method for the preparation of Cu₂O/CuO/ electrochemically reduced graphene oxide (Cu_xO/ERGO) nanostructures by electrochemical growth. The main principle of this method is to simultaneously reduce Cu²⁺, Cu⁺ and graphene oxide in suspension on a gold electrode to achieve the co-precipitation of Cu_xO and ERGO^[44]. The structure of the nanocomposite (Cu_xO/ERGO) can be manipulated by simply changing the electrodeposition voltage and the reaction medium. At the same time, the material shows extremely high electrochemical activity in the detection of AA and dopamine, and can realize the simultaneous detection of AA and dopamine in human body fluid. In addition, metal-organic frameworks (MOFs) formed based on Cu are also good materials for detecting AA. In 2020, Fernandes et al. First used histidine (SSQ-H) to chemically modify octane (3-chloropropyl) siloxane, and the modified material had strong metal ion adsorption properties^[45]. Then adding the modified octaalkyl (3-chloropropyl) siloxane into a solution containing copper ions and stirring to obtain a divalent complex of copper, namely CuHCFSSQ-H. CuHCFSSQ-H showed good electrochemical activity in the detection of AA, with high sensitivity and wide linear detection range, but lacked certain specificity. Metal-organic frameworks (MOFs) are crystalline porous materials with periodic network structure formed by self-assembly of metal ions and organic ligands, which have the characteristics of large specific surface area, regular pore channels and adjustable pore size, and are popular catalytic active materials. In 2022, Xu et al. Synthesized a Cu-TCPP film material based on porphyrin group by mixing copper nitrate and tetraketo acid (4-carboxyphenyl) porphyrin (H₂TCPP) through a simple hydrothermal reaction, and used it for electrochemical detection of AA^[46]. Based on the excellent interfacial self-assembly characteristics and axial coordination effect of H₂TCPP, the synthesized Cu-TCPP thin film material has the characteristics of regular two-dimensional morphology, a large number of exposed active sites, and small diffusion resistance, and shows good electrocatalytic activity in the electrochemical catalytic oxidation of AA. In addition, Liu et al. First reported an Anderson-type polyoxymetallate (POM) -based metal-organic framework materials (POMOFs) containing bis (pyrimidine) -bis (amide) ligands^[47]. The highlight of this work is the successful introduction of bis (pyrimidine) -bis (amide) ligands into POMOFs through a simple hydrothermal reaction to construct a unique topology, as shown in Figure 7. The results showed that POMOFs had multifunctional electrocatalytic activity for AA oxidation and reduction of KBrO₃, potassium nitrite and Cr (VI), and showed high sensitivity and stability in the electrochemical detection of AA, but the specificity needs to be further explored.

Besides copper, other metal compounds such as NiO, TiO₂, MnO₂, ZnO, etc. Are also commonly used materials for the synthesis of electrochemical sensors. Co₃O₄ is a p-type ferromagnetic semiconducting transition metal oxide with corresponding band gaps of 2.10 and 1.60 eV. In Co₃O₄ compounds, Co²⁺ and Co³⁺ ion pairs coexist, in which Co³⁺ occupies octahedral sites and Co²⁺ and oxygen ions occupy tetrahedral sites, forming a close-packed face-centered cubic lattice, and this type of ionic arrangement makes them have excellent electrochemical characteristics^[48]. Khand et al. Synthesized Co₃O₄ by a simple low-temperature thermochemical growth method and modified it with a glassy carbon electrode for the selective determination of ascorbic acid^[49]. In addition to the simple and fast synthesis method, the Co₃O₄/GCE electrode showed good electrochemical properties for the determination of AA in 0. 1 mol/L PBS (0.1 mol/L KH₂PO₄ and K₂HPO₄ mixed solution) at pH 7. 4, with a detection limit as low as 1 μmol/L and a linear range of 0. 05 ~ 3 mmol/L, as well as high stability and selectivity. Tian et al. Successfully prepared Co film modified GCE by electrochemical deposition method, and evaluated the electrochemical performance, stability, pH effect, and kinetic parameters of the redox-active film by electrochemical techniques^[50]. Co/GCE can be used for the quantitative analysis of AA in fruit juice (orange, strawberry, grape), which is rapid and simple, and the results are in good agreement with those obtained by titration with 2,6-dichlorophenol. In addition, Weng et al. Doped Ni in Pt to form a series of Ni-Pt alloy electrodes with different contents of Ni for the detection of AA in human body fluid^[51]. The electrode showed extremely high sensitivity (333μA·cm^-2·mmol·L^-1) in AA detection, and the electrochemical performance was much higher than that of pure Ni or Pt electrodes. The possible mechanism for the superior electrochemical performance of the doped electrode is that Ni, as a modifier, can enhance the specific area of the electrode. Pandikumar et al. Modified the glassy carbon electrode with Fe₃O₄ and graphene to achieve simultaneous detection of dopamine and AA^[52]. The electrochemical sensor based on Fe₃O₄/rGO showed excellent electrocatalytic activity and electron transfer rate for dopamine oxidation. In addition, the sensor electrode showed good sensitivity, selectivity, and low detection limit for the simultaneous detection of dopamine and AA. In addition to the traditional transition metals, which can be used as the active materials for the electrochemical redox of AA, some rare earth metal materials have also been found to have certain electrochemical catalytic activity for AA. In 2019, Huang et al. Reported a nanocomposite composed of thulium phosphate and graphene oxide, and the modified glassy carbon electrode prepared from this material can be used to simultaneously detect ascorbic acid, dopamine and uric acid^[53]. Experiments show that there is a synergistic effect between graphene with good conductivity and thulium phosphate as an electron mediator to accelerate the electron transfer rate. Based on this, the modified glassy carbon electrode shows excellent electrochemical properties in electrochemical detection, with good reproducibility, stability and selectivity. In 2021, Sar Sarıoğulları et al. Prepared a new phthalocyanine using N-ethylcarbazole as a substrate, and reacted Lu³⁺ with phthalocyanine to obtain a coordination compound of Lu^[54]. Experiments show that the coordination compound modified on the glassy carbon electrode can respectively detect AA, dopamine and uric acid in tap water. In addition, complexes of cerium and antimony have also been reported to have certain AA electrocatalytic activity^[55,56]. In 2022, Wang et al. Mixed Ni²⁺ with 2,3,6,7,10,11-hexa-aminotriphenyl hexa-hydrochloride (HITP) ligand to synthesize conductive two-dimensional Ni-MOFs with regular rod-like morphology by hydrothermal method, and developed a portable electrochemical sensor by using the MOFs as electrode sensing materials in combination with integrated circuits and smart phone applications^[57]. Based on the characteristics of highly active Ni-N₄ catalytic sites, two-dimensional superimposed honeycomb lattice and high specific surface area of the material, the sensor device showed good electrochemical activity. In addition, in actual use, the device can send the AA detection data in sweat to the mobile phone software for real-time display through wireless Bluetooth to track and monitor the health status of the human body, as shown in Figure 8. The results showed that the detection limit of the sensor was 1 μmol/L, the sensitivity was 0.814μA·μM^-1·cm^-2, and the linear range was 2 ~ 200 μmol/L.

In order to further improve the performance of AA sensors, multimetallic nanoparticles with multiple functional sites have been widely concerned by scientists. The research value and broad application prospects of multimetallic nanomaterials come from their special physical and chemical properties. The introduction of other metals helps to form intermetallic bonds, which leads to the changes of intermetallic charge transfer/orbital hybridization, particle size, morphology and catalytic properties of multimetallic nanomaterials. Kang et al. Used Au-Ru nanoshells to modify the glassy carbon disc electrode to enhance the ascorbic acid sensitivity^[58]. The Au-Ru nanoshell/GCE shows extremely high stability without adding other auxiliary reagents, and has selectivity, and can accurately determine the concentration of AA in a solution containing uric acid, dopamine, glucose, acetaminophen and NADH interference. Au-Ru nanoshell/GCE can be directly applied to the detection of AA in vitamin C tablets and urine samples. Hou et al. Successfully prepared a multi-metal mixed material containing ZnO nanorods and Au nanoparticles by uniformly attaching Au nanoparticles to ZnO nanorods through a simple in-situ plasma sputtering-assisted method without any template, and modified the material on a glassy carbon electrode to realize the specific detection of AA and uric acid^[59]. The modified electrode showed much better sensitivity and exhibited excellent catalytic activity (sensitivity 40000, linear range: 100 – 40 000 μmol/L). Yin et al. Successfully prepared ordered nanoporous Fe₂O₃/Au films by sputtering and electrochemical deposition based on anodic aluminum oxide template, and subsequently, ITO was soaked in the solution of dissolved Fe₂O₃/Au films to prepare modified electrodes containing Fe₂O₃/Au films^[60]. Experiments show that the sensitivity of the modified electrode is greatly enhanced, and the modified electrode has excellent resistance to interfering biomolecules.

In a word, although metal-based sensors have the advantages of low detection limit, high sensitivity and wide detection range, they can not effectively block the interference of interfering substances to achieve selective detection of AA. Although the selective detection of AA can be achieved by controlling the applied electrocatalytic voltage in the presence of low concentrations of interferents, the electrochemical signal of metal-based sensors is still greatly affected at high concentrations of interferents. Some metals and metal composites with special properties show good selectivity for electrochemical detection of AA, but they also have some defects, such as morphological collapse and chemical structure change caused by extreme environment, which affect the performance of sensors. Therefore, it is still of great significance to find a material with stable chemical properties and specific structure.

3.2.2 Conductive polymer

In recent years, many conductive polymers (such as polyaniline (PANI), polypyrrole (PPy), polythiophene, etc.) have been found to be applied to electrochemical sensors for the selective detection of AA. Polymers are generally not conductive in a neutral environment, while conductive polymers show a certain degree of conductivity because the conjugated backbone can generate charge carriers when doped (oxidized/reduced). Studies have shown that the conductivity of polymers with very low conductivity can be comparable to that of metals or semiconductors after doping. Compared with conventional nanomaterials, conductive polymers have the characteristics of good flexibility, processing in solution, transparency, small mass and low cost. These unique properties make it the material of choice for sensors.

Polyaniline (PANI) and polypyrrole (PPy) are two representative conducting polymers. Experiments show that both of them need to be doped to obtain good conductivity. Without doping, there is a high intramolecular energy level difference between the π-bond molecular orbitals of the polymer, and it is difficult for the π-electron to move across the bond. Both PANI and PPy can be used as sensing materials in ampere, volt-ampere, and conductance/resistance sensors based on the high conductivity exhibited by the conductive polymer after doping^[61]. Based on the electrochemical polymerization of 3,4-dihydroxybenzoic acid (3,4-DHBA) and aniline, Sun et al. Prepared PANI and 3,4-DHBA self-doped polymer modified gold electrode on a microdisk gold electrode^[62]. The experimental results show that the gold electrode modified by the conductive polymer has high sensitivity for AA detection, and has a wide linear detection range and a fast and stable current response. The mechanism of the electrocatalytic reaction may be that AA diffuses to the electrode surface and reacts with the electroactive couple of the copolymer, resulting in a current response and an increase in the current value. Ambrosi et al. Drop-cast dodecylbenzenesulfonic acid (DBSA) -doped polyaniline nanoions onto a screen-printed carbon paste electrode to prepare an ascorbic acid sensor^[63]. The sensor showed good selectivity and sensitivity at neutral pH and 0 V (vs Ag/AgCl). The mechanism of AA response is the oxidation and hydrolysis of AA by polyaniline. At neutral pH, DBSA-doped PANI exists in the conducting semi-reduced oxidized form of PANI (PANI⁺), while the presence of dopant (A^-) can form an electrically neutral state with it. Subsequently, the two oxidation States of polyaniline (2PANI⁺) are reduced by AA, which is oxidized to dehydroascorbic acid. Finally, the reduced neutral polyaniline (2PANI⁰) was reoxidized at the electrode at the appropriate anodic potential, as shown in Fig. 9 B.

By changing the type of dopant, the obtained conductive polymer will also show different electrochemical properties. Gao et al. Studied the electrochemical reaction of ascorbic acid at polypyrrole/dodecyl sulfate film electrode (PPy/DS)^[64]. The results showed that the catalytic oxidation of AA occurred at the interface between the PPy/DS film and the solution, not on the substrate electrode, and the electrochemical oxidation peak of AA appeared at a more negative potential (0. 3 V) than that of the modified electrode, which further indicated that PPy had electrocatalytic activity. In addition, Chen et al. Modified the gold electrode by PPy and 4-hydroxy-6-methyl-2-mercaptopyrimidine (HMMP)^[65]. Compared with the PPy/Au electrode and the bare gold electrode, stronger reaction kinetics, current response, and reproducibility can be observed on the PPy/HMMP/Au electrode. In addition to the synthesis of conducting polymers with different electrochemical properties by selecting different dopants, compounding conducting polymers with metal nanoparticles, metal oxides and carbon nanomaterials is also an effective way to change the electrochemical properties of polymers. Based on the modification of ZnO nanoparticles on glassy carbon electrode, Kumar et al. Used the modified electrode as the working electrode to polymerize and deposit poly-luminol (3-aminophthalhydrazide) by electrochemical method, and successfully prepared the nano-zinc oxide/poly-luminol mixed film modified electrode, which was successfully applied to the detection of AA in drugs^[66]. Compared with the polyluminol film modified electrode, the electrode has higher sensitivity and lower catalytic potential (0. 1 V vs Ag/AgCl). The possible reason is that the specific surface area of the modified electrode is increased to a certain extent after the addition of ZnO nanoparticles, which greatly enhances the adsorption capacity of the electrode for the detected substance. Based on the electropolymerization principle of pyrrole and the deposition principle of gold nanoparticles, Babu et al. Prepared a AuNP-PPy/TiO₂ electrode by controlled cyclic voltammetry electrodeposition, which has a sensitivity of up to 63.912μA·mM^-1·cm^-2, a linear range of 1 μmol/L – 5 mol/L, and good selectivity, and has been successfully applied to the detection of AA in fruits^[67]. Zhang et al. Synthesized PANI/SiW₁₂-CNT/GCE electrode by one-step electropolymerization of aniline containing suspended silicotungstic acid and carbon nanotubes on the surface of glassy carbon electrode rapidly and simply^[68]. The simultaneous doping of metal oxide and carbon nanotubes made the modified electrode show the advantages of low detection limit (0. 51 μmol/L), good repeatability, high stability and strong selectivity, and excellent performance in the detection of AA concentration in fruit juice. Puangjan et al. Successfully attached the nanocomposite nanomaterial MnO₂-SbO₂ on the doped tin oxide electrode containing PANI film by a simple potentiostatic deposition method, and the modified electrode could realize the simultaneous detection of AA and Acetylsalicylic acid (AsA), and showed an extremely low detection limit and a wide detection range^[69].

With the development of research on conducting polymers, more and more polymers with special electrochemical properties have been found. Ensafi et al. Placed the polished and electrochemically pretreated glassy carbon electrode in a mixed solution containing 0.2 mol/L NaOH and 1.0 mmol/L sulfonazo Ⅲ, and applied cyclic potential scanning for 20 times in the range of − 0.10 – 1.20 V at a scanning rate of 100 mV·s^-1, and prepared a sensing material capable of simultaneously detecting AA, dopamine, and uric acid by electrochemical polymerization^[70]. The material has achieved satisfactory results in the detection of AA, dopamine and uric acid in dopamine injection, vitamin C tablets and human urine, showing good selectivity and sensitivity. Chethana et al. Modified the carbon paste electrode with methionine to successfully reduce the overpotential of bare carbon paste electrode for AA detection, and effectively improved the detection sensitivity and reaction rate^[71]. Taei et al. Modified a layer of poly (4-chloro-3-iodobenzotrifluoride) (trypan blue) film on the glassy carbon electrode, which not only effectively separated the potential signals of AA, norepinephrine (NA), acetaminophen (AC) and tryptophan (Try) in electrochemical detection, but also increased the oxidation current of AA, NA, AC and Try by 11.0, 7.0, 1.4 and 3.8 times, respectively, and successfully applied to the detection of AA, NA, AC and Try in pharmaceutical and biological samples^[72]. In addition, controlling the morphology and structure of polymers is also one of the methods to improve the performance of polymer sensors. In 2021, Shi et al. Used a novel liquid-liquid interfacial polymerization method to grow polyaniline film on a two-dimensional graphene-loaded glassy carbon electrode^[73]. The interfacial polymerization can effectively inhibit the secondary growth of the polymer, and the SEM characterization results show that the polyaniline film grown by this method is uniform and regular, and shows good two-dimensionality. The test results show that the material has good electrochemical performance in the aspect of electrochemical detection of AA, and has excellent reproducibility and stability. In the same year, Wang et al. achieved precise control of polymer structure through molecular imprinting technology, and developed a molecularly imprinted polymer (MIP) -based electronic tongue with specific detection by combining molecularly imprinted polymer and electrochemical sensor, as shown in Fig. 10^[74]. A molecularly imprinted polymer sensor templated by ascorbic acid was prepared by in situ electropolymerization of pyrrole as a polymer monomer in the presence of p-toluenesulfonic acid anion. Among them, p-toluenesulfonic acid anion is used as a functional dopant of polypyrrole molecularly imprinted polymer to improve the conductivity, mechanical properties, durability, and control the microporous structure of the polymer. The electrochemical detection results showed that the sensor had good specificity and sensitivity for AA.

To sum up, on the premise of the complex structure and good stability of the polymer itself, the stability, selectivity and sensitivity of the sensor can be significantly optimized by introducing and doping noble metal nanoparticles, transition metal oxides and modification groups into the polymer material. In addition, it is also an effective way to optimize the sensor by controlling the morphology and structure of the conducting polymer through the synthetic pathway. However, there are still some problems in using conductive polymers as sensor materials, such as the lack of research on the principle of selective detection of conductive polymers, and the lack of in-depth research on the influence of polymer properties (morphology, degree of polymerization, etc.) On the sensing performance of materials.

3.2.3 Carbon material

Carbon nanomaterials (such as fullerenes, carbon nanotubes, nanodiamonds and graphene sheets) with wide availability, corrosion resistance and unique surface properties have gradually developed into good materials to replace metal-based catalytic materials in many application fields, and have shown great potential in the field of electrochemical sensing. The carbon atoms in graphene are bonded by sp² hybrid orbitals, and the σ bond connects with the carbon atoms to form a honeycomb layered structure of hexagonal rings, while the pz orbital in the vertical direction of the carbon atoms forms a large π bond throughout the whole layer. This unique structure gives it excellent conductivity. In addition, graphene has the characteristics of enhancing bioactivity and biocompatibility by implanting carboxyl ions through a simple chemical process^[75]. Sheng et al. Used N atoms to chemically dope graphene to realize the adjustment of electronic characteristics and surface chemical properties of graphene materials, construct special chemical structures and enhance their electronic characteristics^[76]. Nitrogen-doped graphene sheets (NG) with a thickness of about 0. 8 nm were successfully prepared by thermal annealing of the mixture of graphite oxide and melamine, and the electrochemical sensor based on NG can simultaneously detect AA, dopamine, uric acid and other small biological molecules. Further experiments show that NG/GCE can simultaneously detect AA, dopamine and uric acid with good sensitivity and selectivity, which is mainly due to the different strength of π-π bonds and hydrogen bonds formed between the target biomolecule and NG. Qi et al. Successfully constructed a new electrochemical sensor based on pristine graphene (PG) to simultaneously detect AA, uric acid and dopamine through a simple chemical method^[77]. Compared with bare glassy carbon electrode and s-GR/GCE, PG/GCE exhibits excellent electrochemical performance (conductivity up to 13760 S·m^-1) due to its extremely low oxygen content and defect-free structure. Li et al. successfully prepared a graphite-doped carbon paste electrode (G/CPE) by simply grinding paraffin oil, graphite and graphene in a mortar. Based on the high conductivity of graphene, the electrode showed good electrochemical properties in AA detection, with a detection limit as low as 0.07 μmol/L and a linear range of 0.1 μmol/L ~ 0.106 mmol/L^[78]. In 2020, Jiang et al. Reported a ratiometric electrochemical sensor (RECS) (Fig. 11) for online repeated measurement of AA in brain microdialysate in vivo^[79]. The sensor is constructed by electrodepositing graphene oxide (GO) on a glassy carbon electrode, and methylene blue (MB) is electrostatically adsorbed on the surface of GO as a built-in reference material of the sensor to realize the ratiometric detection of AA. During the detection, the oxidation of AA at a relatively negative potential (-100 mV) and the oxidation of MB at a separation potential (-428 mV) were achieved by applying appropriate electroreduction potentials. In vitro experiments showed that RECS had high sensitivity (detection limit: 10 nmol/L), certain selectivity and good stability for AA detection. The sensor successfully monitored intracranial AA concentration during global cerebral ischemia-reperfusion. In 2021, Sordan et al. Developed a miniature sensor chip for rapid detection of AA based on graphene materials and microfluidic technology^[80]. The sensor chip uses an Ag electrode printed by silver ink as a counter electrode, and an Ag electrode deposited with graphene as a working electrode. A microfluidic channel fabricated by Xurography technique was constructed between two Ag electrodes. Experiments show that the sensor chip can successfully distinguish AA and isomaltose solution injected into the microfluidic channel, and the addition of graphene can improve the detection sensitivity by 5. 28% and reduce the detection limit by 12% compared with the chip without graphene deposition. Diao et al. Reported a metal-free three-dimensional nitrogen-doped graphene-based electrochemical sensor for the simultaneous determination of AA, dopamine, uric acid, and acetaminophen^[81]. The 3D N-doped graphene material with 3D porous structure and N-doping effect in the sensor can provide a multi-dimensional electron transfer pathway, and then improve its electrocatalytic activity to distinguish the four analytes. The experimental results showed that the linear concentration range of AA was 20 ~ 10000 μmol/L and the detection limit was 3. 91 μmol/L for the determination of one analyte alone. When the concentrations of four analytes changed synchronously, the detection of AA was interfered, the detection range was reduced and the detection limit was increased. Currently, the sensor has been successfully used to monitor AA, dopamine, uric acid, and acetaminophen in human urine samples. In 2022, Yang et al. Combined covalent organic framework materials (COFs), gold nanoparticles and redox graphene to prepare an electrochemical sensor for the simultaneous detection of uric acid, dopamine and AA^[82]. The results show that the introduction of redox graphene and the deposition of gold nanoparticles on COFs can effectively improve the electrocatalytic activity and stability of the composite. The detection limits of the sensor for uric acid, dopamine and AA were 0.07, 0.03 and 4.30 μmol/L, respectively.

Different from two-dimensional graphene, carbon nanotube (CNT) is a kind of quantum material with one-dimensional characteristics, in which carbon atoms are arranged in a hexagonal pattern to form coaxial circular tubes with several to tens of layers, the distance between two adjacent layers is about 0. 34 nm, and the diameter is 2 to 20 nm. The special structure of carbon nanotubes makes them have specific mechanical, electrical and chemical properties. Bijad et al. Supported ZnO on CNT by chemical deposition method to prepare a modified ZnO/CNT/CPE electrode, which greatly improved the sensitivity of the electrode to AA. The detection limit is as low as 0.07 μmol/L, and the linear range is as wide as 0.1 ~ 450 μmol/L. It can be used to detect AA in green vegetable juice and fruit juice^[83]. Naqvi et al. Loaded iron and nickel nanocomposites on CBT and successfully constructed Fe, Ni/CNTs/GCE for simultaneous detection of AA, hydrogen peroxide and glucose^[84]. The electrode showed excellent sensitivity, stability, and repeatability, and the detection efficiency did not fluctuate significantly after 30 cycles of testing. Ramakrishnan et al. Used radio-frequency chemical vapor deposition to synthesize platinum nanoparticle-modified graphene and carbon nanotube materials (Pt-Gr-CNT) in one step using Pt/MgO as a catalyst^[85]. Due to the excellent electrical conductivity and ultra-high electroactive surface area of graphene and CNT, the prepared electrode showed extremely high sensitivity (0.186μA·μM^-1·cm^-2) in the detection of AA in vitamin C tablets, human serum, urine, with a detection limit as low as 50μmol/L.

CNT and graphene are the two most common carbon materials in the field of electrochemical sensors. In addition, fullerene (C₆₀) and carbon fiber can also be used to prepare electrochemical sensors^[86⇓~88]. Fullerene is an electron-withdrawing 3D nanomaterial that reversibly accepts multiple electrons to generate stable polyanionic intermediates. The partially reduced fullerene has strong conductivity and can be used as a modified electrode for the detection of various organic compounds and biomolecules. Zhang et al. Constructed a stable electrochemical biosensor by electrodepositing platinum nanosheets on a C₆₀ modified glassy carbon electrode for simultaneous detection of AA, DA, and UA, and the modified electrode showed stronger electrocatalytic performance (LOD: 0.43 μmol/L, linear range: 10 – 1800 μmol/L) compared with the unmodified electrode^[89]. In addition, many carbon materials with different properties have been gradually developed. In 2021, Culeddu et al. Prepared a highly active carbon material by thermochemical reaction of graphene, and prepared a carbon screen printed sensor for AA detection based on this material. The sensor can detect AA in fresh-cut fruits, and its sensing performance is better than that of multi-walled carbon nanotubes (the active area is increased by 1.4 times, and the sensitivity is about 2 times that of multi-walled carbon nanotubes)^[90]. Lin et al. Prepared three-dimensional nitrogen-doped hierarchical porous carbon materials by carbonized cellulose nanocrystals and urea, and constructed a novel electrochemical sensor based on them for the selective detection of AA^[91]. The experiments show that the presence of porous carbon can increase the electron transport between the analyte and the sensing electrode, while significantly reducing the overpotential of AA oxidation compared with the bare glassy carbon electrode. The detection limit of the sensor for AA was 0. 25 μmol/L, the detection range was 80 μmol/L ~ 10 mmol/L, and the sensitivity was 0.1138μA·μM^-1·cm^-2. In 2022, Chen et al. Prepared an N-doped carbon nanosheet/3D porous carbon (3D-KSC/C_CSBP) nanocomposite by carbonizing the vertically grown Schiff base foam on 3D porous carbon, and the Schiff base foam was produced by ammonia aldehyde condensation between p-benzaldehyde and hydrazine hydrate, which can be a good N source, as shown in Fig. 12^[92]. The experimental results show that the sensor constructed by the material can simultaneously detect AA, dopamine and uric acid, the detection limit for AA is 0. 66 mmol/L, and the linear range is 1. 98 ~ 6 mmol/L.

To sum up, carbon-based electrochemical sensors have the advantages of good biocompatibility, high sensitivity, good stability, and simultaneous detection of multiple substances, showing great application potential in the field of sensors. However, the mechanism of electrocatalytic oxidation of AA by carbon-based materials is still unclear. In addition, studies have shown that sensors based on carbon materials can generally respond to a variety of small biomolecules. Although simultaneous detection of multiple substances can be achieved by applying different voltages, if the reagent to be detected contains a variety of small biomolecules with high concentrations, the electrochemical response will interfere with each other and accurate analysis results cannot be obtained. Therefore, it is of great significance to regulate the material structure by doping heteroatoms or combining with other substances with special structures to eliminate the response of sensing materials to interferents.

With the in-depth study of sensor materials, more and more new materials have been developed. In addition to carbon nanomaterials modified electrodes, pure metal/metal oxide modified electrodes and conductive polymer modified electrodes, other substances (such as boron nitride, COF, metal sulfides, etc.) Have also been found to have good electrochemical performance and can be used for AA detection in different environments^[93]. Cabrita et al. Modified nanocrystalline semiconductor bismuth sulfide nanoparticles on titanate nanofibers to construct a new material with electrocatalytic properties. Based on the electrochemical hydrogen storage ability of Bi₂S and its special Li⁺ intercalation ability, the catalytic oxidation ability of the electrode for AA was enhanced, and AA detection at lower potentials could be achieved^[94]. The sensor has a detection range of 0.1 – 10 mmol/L and a sensitivity of 38μA·mM^-1·cm^-2. In 2021, Ye et al. Developed an electrochemical sensor for simultaneous detection of AA, dopamine, and uric acid based on the synergistic effect of gold nanoparticle-doped carboxylated covalent organic framework (ACOF) and poly (fuchsin) film^[95]. Based on the hydrogen bonding and electrostatic interactions between the three compounds and materials, the sensor shows good electrochemical properties, and has the advantages of hydrophilicity and selectivity.

4 Conclusion and prospect

In this paper, the electrochemical detection of AA is comprehensively reviewed, the characteristics and defects of different sensor electrode materials are analyzed, and the different characteristics of AA sensors constructed by different materials are summarized (see Table 1): For enzyme sensors, the most prominent problem is the sensitivity of the enzyme to the detection environment. This can lead to rapid sensor deactivation and performance distortion; Second, although ascorbate oxidase is widely available, the enzyme is expensive to extract and purify. Moreover, the method of enzyme immobilization on the substrate lacks generality. For sensors based on metal, conductive polymer and carbon materials, the most prominent problem is that these sensors have low selectivity and can not achieve specific catalysis of ascorbic acid. Secondly, there are many materials that can be used in enzyme-free sensors, and the environmental applicability of various materials is not the same, so there is a lack of a unified evaluation standard for the performance of sensors. On the other hand, the influence mechanism of material morphology and chemical structure on sensor performance is still unclear, and few articles have systematically and comprehensively explained the structure-activity relationship between materials and properties.

In a word, amperometric AA electrochemical detection has the characteristics of fast response, wide linear range and high sensitivity, and can realize portable, wearable and integrated continuous real-time monitoring, which has great practical application value. It is of great scientific and engineering significance to develop sensors with good selectivity and application in complex environments, as well as to develop simple, low-cost, modular synthesis and integration methods. Based on the above problems in the field of AA sensing, future research on AA sensors can focus on the following three aspects: 1) to clarify the structure-activity relationship between materials and sensor performance. The electrochemical behavior of different nanoscale and atomic scale materials was studied, and the reaction mechanism between AA and sensor materials was explored by means of computational simulation and simulation. 2) Develop the universality of AA sensing materials, modular synthesis and integration methods, realize the large-scale preparation of sensing materials and devices, and obtain the change law of material performance with time, temperature, pH and other external environments through a large number of sensor electrochemical detection experiments, so as to complete the accurate calibration of AA sensors. 3) Develop sensing devices that can be applied to a wider range of scenarios, such as combining AA sensing materials with intelligent terminals, developing wearable or implantable flexible sensing materials, and realizing the tracking and detection of AA concentration in sweat, serum or human tissues.

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