An electrochemical sensor for detecting dopamine with anti-interference, preparation method and application

Abstract

The application belongs to the technical field of bioelectrochemical sensors, and particularly relates to an anti-interference dopamine detection electrochemical sensor, a preparation method and application. The application constructs a gold-doped conductive polymer composite sensing function layer on the surface of an electrode substrate, utilizes the synergistic electrochemical effect between gold nanoparticles and the conductive polymer, optimizes the microstructure of the electrode interface, accelerates the interface electron transfer rate, enhances the electrochemical response capability of the sensor to dopamine, and improves the structural stability of the sensing interface, detection repeatability and electrode service life. The application introduces a poly(3-acetyl thiophene) functional modification layer as a specific anti-interference interface, utilizes the space screening effect and charge selective repulsion characteristics, can shield the coexisting non-target electroactive interference molecules such as ascorbic acid and uric acid in the biological matrix, improves the anti-bioadsorption and anti-passivation capacity of the electrode, and solves the technical problems of low dopamine detection accuracy and poor anti-interference performance in a complex living biological environment.

Description

Technical Field

[0001] This invention relates to the field of bioelectrochemical sensor technology, and more specifically, to an electrochemical sensor for detecting dopamine with anti-interference capabilities, its preparation method, and its application. Background Technology

[0002] Neurotransmitters (NTs) are a class of key neuroactive substances in the nervous system, acting as chemical messengers to mediate signal transmission between neuronal synapses. Released from the presynaptic membrane, these substances bind to specific receptors on the postsynaptic membrane, regulating the excitation and inhibition processes of postsynaptic neurons and serving as core mediators for maintaining the normal physiological functions of the central nervous system. Among them, dopamine (DA), as one of the most important catecholamine neurotransmitters in the central nervous system, is widely involved in the fine regulation of various physiological processes, including motor regulation, emotional cognition, endocrine regulation, and reward effects. Studies have shown that abnormalities in the synthesis, metabolism, and release levels of the dopaminergic neurotransmitter system in the brain are closely related to the occurrence, development, and outcome of various central nervous system diseases, such as Parkinson's disease (PD), Alzheimer's disease (AD), schizophrenia, depression, and drug addiction. Therefore, achieving efficient and accurate monitoring of dopamine release dynamics has significant basic research value and clinical application significance for the early diagnosis, pathological mechanism analysis, disease progression assessment, and drug efficacy evaluation of neurological diseases.

[0003] Currently, conventional methods for dopamine detection mainly include spectrophotometry, capillary electrophoresis, high-performance liquid chromatography (HPLC), chemiluminescence, and fluorescence analysis. While these traditional detection techniques offer high sensitivity and selectivity in in vitro samples, they are essentially offline detection methods. They typically require multiple pretreatment and separation steps, including sample collection, protein precipitation, extraction and enrichment, chromatographic separation, and derivatization labeling. This results in cumbersome and lengthy procedures, high operational complexity, and long analysis times, making it difficult to meet the real-time tracking requirements. More importantly, these methods cannot achieve continuous real-time tracking of dopamine release dynamics in vivo, making it difficult to capture transient changes in dopamine concentration in the synaptic cleft on millisecond to second timescales. This significantly hinders in-depth research into the underlying mechanisms of dopamine-related neurological diseases.

[0004] Electrochemical sensors, with their unique advantages of high spatiotemporal resolution, flexible and diverse detection modes, fast response speed, high sensitivity, and outstanding miniaturization potential, provide a promising technical path for real-time, in-situ, and in vivo dynamic monitoring of dopamine. In particular, implantable electrochemical sensors constructed using microelectrodes or microarray electrodes can be directly implanted into target brain regions. By applying appropriate potentials, they can achieve real-time recording of dopamine oxidation currents, enabling real-time tracking of dynamic changes in dopamine release in specific brain regions of living animals. This has gradually become a research hotspot and development direction in the field of in vivo neurochemical analysis.

[0005] However, existing electrochemical sensing technologies still face a series of technical bottlenecks that urgently need to be overcome when applied to dopamine detection in complex biological environments: First, the coexistence of electroactive interfering substances severely affects the accuracy and selectivity of detection. High concentrations of various electroactive small molecules, such as ascorbic acid (AA), uric acid (UA), and 3,4-dihydroxyphenylacetic acid (DOPAC), are commonly found in the brain tissue microenvironment and complex biological fluids such as cerebrospinal fluid and blood. The electrochemical oxidation potentials of these interfering substances highly overlap with the oxidation potential of dopamine (both within the range of +0.1 V to +0.3 V vs. Ag / AgCl). When using conventional bare electrodes or traditional monolayer modified electrodes for detection, the electrochemical response signals of the interfering substances and dopamine are severely superimposed. The high background interference signal significantly masks the low-concentration true response signal of dopamine, resulting in an extremely low signal-to-noise ratio. Therefore, the accuracy, reliability, and reproducibility of dopamine detection data cannot be guaranteed. Although some researchers have attempted to use cation exchange membranes such as Nafion as anti-interference coatings to block negatively charged interfering substances using the Donnan repulsion effect, such coatings generally suffer from problems such as uneven membrane thickness, poor long-term stability, non-specific adsorption of dopamine cations, and mass transfer hindrance, making it difficult to exert anti-interference functions in actual in vivo detection in a long-term, stable and effective manner.

[0006] Secondly, the electrode interface structure suffers from poor stability, and the modification layer is prone to detachment, limiting its service life. Existing sensor interface modification materials (including carbon-based conductive materials, metal oxides, two-dimensional conductive materials, and conventional conductive polymers) generally have weak adhesion to the electrode substrate. They are mostly attached to the electrode surface using physical drop-coating, dip-coating, or simple electrodeposition methods. Interface bonding relies primarily on physical adsorption or weak chemical interactions, lacking strong chemical bonding anchoring. During long-term in vivo detection, factors such as brain tissue micromovement, cerebrospinal fluid flow, and the volume expansion and contraction stress generated by repeated electrochemical oxidation-reduction processes cause the modification layer to easily peel off, detach, or crack, leading to structural failures. This directly results in a sharp reduction in the number of active sites at the sensor interface, a drastic drop in electron transport capacity, and a significant attenuation of the detection signal. The electrode service life is generally short (typically only a few hours to tens of hours of stable operation), far from meeting the long-term in vivo dynamic monitoring needs of neuroscience research, which can last for several days to weeks.

[0007] Third, the accumulation of oxidation products leads to electrode passivation and deterioration of detection repeatability. After dopamine undergoes an electrochemical oxidation reaction on the electrode surface, the resulting intermediate oxidation product—dopamine-ortho-quinone—has extremely high chemical reactivity. It readily undergoes subsequent intermolecular cyclization polymerization on the electrode surface or addition reactions with the solution matrix components, forming a non-conductive black polymer insulating film (the so-called "electrode contamination" or "electrode passivation layer"). The continuous deposition and coverage of this passivation layer on the electrode surface leads to the gradual deactivation of electrode active sites, a continuous increase in interfacial electron transfer resistance, and a continuous decay and drift of the detection response signal. This manifests as poor signal repeatability and large standard deviation in repeated detections or reuse of the same electrode, failing to accurately reflect the true concentration changes of dopamine. Especially in in vivo continuous monitoring scenarios, signal drift caused by electrode passivation is often misinterpreted as true fluctuations in physiological concentration, seriously interfering with the reasonable interpretation of experimental data and the accurate extraction of pathophysiological patterns.

[0008] In summary, existing electrochemical sensing technologies for in vivo dopamine detection in complex biological matrices are limited by multiple technical shortcomings, including poor anti-interference specificity, weak interface stability, insufficient passivation resistance, and poor detection repeatability. These limitations hinder the long-term, stable, and accurate detection of dopamine in vivo, severely restricting basic research progress and clinical translational applications in dopamine-related neurological diseases. Therefore, there is an urgent need for systematic innovation at the source level, including material selection, structural design, and fabrication processes at the sensing interface, to develop an electrochemical sensor for in vivo dopamine monitoring that combines high sensitivity, excellent anti-interference capability, strong interface stability, and long-term passivation resistance. This would meet the pressing needs of cutting-edge neuroscience research and clinical auxiliary diagnosis for high-performance dopamine detection technology. Summary of the Invention

[0009] In view of this, the present invention addresses the deficiencies of the prior art by providing an electrochemical sensor for detecting dopamine that effectively shields interference signals from complex matrices in living organisms, significantly improving the sensitivity, stability, and anti-interference capability of dopamine detection in vivo, along with its preparation method and application.

[0010] To solve the above problems, this application adopts the following technical solution: One objective of this application is to provide an electrochemical sensor for detecting dopamine with resistance to interference, comprising: Base electrode; A composite sensing functional layer is disposed on the surface of the substrate electrode. The composite sensing functional layer has a core-shell structure, which includes gold nanoparticles and a conductive polymer coated on the surface of the gold nanoparticles. An anti-interference protective layer is disposed on the outer surface of the composite sensing functional layer, and the anti-interference protective layer is a poly(3-thiophene acetate) layer.

[0011] In some embodiments, the gold nanoparticles and the conductive polymer are connected by a carboxyl-containing linker, one end of which is bound to the gold nanoparticles via a thiol group, and the other end of which is bound to the conductive polymer via a carboxyl group.

[0012] In some embodiments, the linker is a carboxylated alkyl sulfide, preferably any one or more of 3-mercaptopropionic acid, mercaptooctanoic acid, or mercaptodecanoic acid.

[0013] In some embodiments, the conductive polymer is any one of poly(3,4-ethylenedioxythiophene), polythiophene, or polypyrrole.

[0014] In some embodiments, the base electrode is any one of a platinum electrode, a gold electrode, or a carbon-based electrode.

[0015] The second objective of this application is to provide a method for preparing the aforementioned interference-resistant electrochemical sensor for detecting dopamine, comprising the following steps: Provide a base electrode; A core-shell composite sensing functional layer is formed on the surface of the substrate electrode. The composite sensing functional layer includes gold nanoparticles and a conductive polymer coated on the surface of the gold nanoparticles. A poly(3-thiophene acetate) anti-interference protective layer is formed on the outer surface of the composite sensing functional layer.

[0016] In some embodiments, the formation of the composite sensing functional layer includes: Gold nanoparticles were prepared on the surface of the substrate electrode using an electrochemical deposition method. Electrodes modified with gold nanoparticles were placed in a solution containing carboxyl alkane sulfides for self-assembly, thereby introducing carboxyl groups onto the surface of the gold nanoparticles. The self-assembled electrode was placed in a conductive polymer monomer solution for electrochemical polymerization, forming a conductive polymer coating layer on the surface of the gold nanoparticles, thus obtaining a core-shell structured composite sensing functional layer.

[0017] In some embodiments, the electrochemical deposition method uses a deposition voltage of -0.1 V to -0.5 V and a deposition time of 20 s to 60 s; preferably, the electrochemical deposition method is any one of constant potential electrodeposition, pulse electrodeposition, or cyclic voltammetric deposition. And / or, the self-assembly time is 12 h to 24 h; And / or, in the electrochemical polymerization, the polymerization voltage is 1.0 V to 1.5 V, and the polymerization time is 100 s to 400 s.

[0018] In some embodiments, the formation of the poly(3-thiophene acetate) anti-interference protective layer includes: placing an electrode with a composite sensing functional layer in a 3-thiophene acetate solution, and forming a poly(3-thiophene acetate) anti-interference protective layer on the outer surface of the composite sensing functional layer by electrochemical polymerization.

[0019] In some embodiments, prior to forming the composite sensing functional layer, the substrate electrode is pretreated by oxygen plasma treatment followed by cyclic voltammetry scanning in an acid solution until the curve stabilizes, in order to purify and activate the electrode surface.

[0020] In some embodiments, after forming the poly(3-thiophene acetate) anti-interference protective layer, an activation process is further included: the resulting electrode is activated by cyclic voltammetry in a buffer solution until the electrochemical response curve is stable.

[0021] A third objective of this application is to provide an application of the electrochemical sensor for detecting dopamine with resistance to interference, or the electrochemical sensor for detecting dopamine with resistance to interference prepared according to the method described, in at least one of the following (a) to (d): (a) Preparation of a detection product for detecting dopamine in complex biological samples; (b) Prepare detection products for detecting catecholamines; (c) Develop products for dynamic monitoring of pathological models of Parkinson's disease and / or depression; (d) Prepare detection products for the detection of dopamine or phenolic substances in the environment or food.

[0022] The present application adopts the above technical solution, and its beneficial effects are as follows: The electrochemical sensor for dopamine detection provided in this application utilizes a gold-doped conductive polymer composite sensing functional layer constructed on the electrode substrate surface. By leveraging the synergistic electrochemical effect between gold nanoparticles and the conductive polymer, the microstructure of the electrode interface is effectively optimized, and the interfacial electron transfer rate is accelerated, significantly enhancing the sensor's electrochemical response to dopamine and greatly improving the structural stability, detection repeatability, and electrode lifespan. Furthermore, this invention introduces a poly(3-acetylthiophene) functional modification layer as a specific anti-interference interface. Utilizing its unique spatial sieving effect and charge-selective repulsion characteristics, it can efficiently shield coexisting non-target electroactive interfering molecules such as ascorbic acid and uric acid in biological matrices. Simultaneously, it significantly improves the electrode's resistance to bioadsorption and passivation, effectively solving the technical challenges of low accuracy and poor anti-interference performance in dopamine detection under complex living biological environments. This invention employs a layered composite modification strategy to construct an integrated multifunctional sensing interface, which balances high detection sensitivity, excellent anti-interference performance, and detection stability. It enables real-time, in-situ, and accurate detection of dopamine in complex biological samples and in vivo environments, making it suitable for practical applications in the study of neurological disease mechanisms and clinical auxiliary detection. Attached Figure Description

[0023] To more clearly illustrate the technical solutions of the embodiments of this application, the drawings used in the description of the embodiments of this application or the prior art will be briefly introduced below. Obviously, the drawings described below are only some embodiments of this application. For those skilled in the art, other drawings can be obtained based on these drawings without creative effort.

[0024] Figure 1 This is a schematic flowchart of the rapid fluorescence lifetime imaging method provided in an embodiment of the present invention.

[0025] Figure 2 This is a schematic diagram of the structure of the rapid fluorescence lifetime imaging device provided in an embodiment of the present invention.

[0026] Figure 3 This is a schematic diagram of the operation of the rapid fluorescence lifetime imaging device provided in Embodiment 1 of the present invention.

[0027] Figure 4 The measured characteristic curves of amplitude ratio (left) and phase difference (right) provided in Embodiment 1 of the present invention.

[0028] Figure 5 Fluorescence lifetime diagrams of the CY3 (left), RHB (middle), and TR (right) standard fluorescent solutions provided in Example 1 of this invention. Detailed Implementation

[0029] The embodiments of this application are described in detail below. Examples of these embodiments are shown in the accompanying drawings, wherein the same or similar reference numerals denote the same or similar elements or elements having the same or similar functions throughout. The embodiments described below with reference to the accompanying drawings are exemplary and intended to explain this application, and should not be construed as limiting this application. In the description of this application, it should be understood that the terms "upper", "lower", "horizontal", "inner", "outer", etc., indicate the orientation or positional relationship based on the orientation or positional relationship shown in the accompanying drawings, and are only for the convenience of describing this application and simplifying the description, and do not indicate or imply that the device or element referred to must have a specific orientation, or be constructed and operated in a specific orientation, and therefore should not be construed as a limitation of this application. Furthermore, the terms "first" and "second" are used for descriptive purposes only and should not be construed as indicating or implying relative importance or implicitly specifying the number of technical features indicated. Thus, a feature defined as "first" or "second" may explicitly or implicitly include one or more of that feature. In the description of this application, "multiple" means two or more, unless otherwise explicitly specified. To make the objectives, technical solutions, and advantages of this application clearer, the following detailed description is provided in conjunction with the accompanying drawings and embodiments.

[0030] Please see Figure 1 The electrochemical sensor for detecting dopamine with anti-interference capability provided in this application includes: a substrate electrode 110, a composite sensing functional layer 120, and an anti-interference protective layer 130. The specific implementation scheme of each layer is described in detail below.

[0031] The substrate electrode 110, serving as the basic carrier unit of the sensor, is made of a conductive material with excellent conductivity, a wide electrochemical window, and good biocompatibility. After oxygen plasma treatment and sulfuric acid cyclic voltammetry activation pretreatment, the electrode surface forms a clean micro-surface rich in active sites, providing an ideal substrate for the stable attachment of subsequent functional layers.

[0032] Specifically, the substrate electrode is any one of a platinum electrode, a gold electrode, or a carbon-based electrode. Platinum electrodes are chosen as the detection substrate because they possess excellent conductivity and strong electrochemical inertness, providing a basic support for the stable adhesion of multilayer functional thin films. First, the electrode substrate is treated with oxygen plasma for 180 s, and then cyclic voltammetry is performed on the electrode in a 0.5 mol / L sulfuric acid solution. The scanning voltage range is -0.2 V to 1.5 V, and the scanning continues until the cyclic voltammetry curve stabilizes. This process purifies and activates the platinum electrode surface, removes surface contaminants and unstable oxide films, reduces the substrate background signal, and optimizes the interfacial bonding performance of the modified material.

[0033] It is understandable that the aforementioned electrode materials are the most commonly used working electrode materials in the field of electrochemical analysis, possessing common characteristics such as excellent conductivity, wide electrochemical window, and low background current. After oxygen plasma treatment and sulfuric acid cyclic voltammetry activation, the surfaces of various electrodes can expose clean micro-interfaces rich in active functional groups (such as oxygen-containing groups), which is sufficient to support the electrochemical nucleation and growth of gold nanoparticles.

[0034] The composite sensing functional layer 120 is disposed on the surface of the substrate electrode 110. The composite sensing functional layer 120 has a core-shell structure, which includes gold nanoparticles and a conductive polymer coated on the surface of the gold nanoparticles.

[0035] In this embodiment, this layer is disposed on the surface of the substrate electrode and is the core sensing element of the present invention. It has a clearly defined "shell-core" spatial configuration, specifically including: The core layer consists of gold nanoparticles, generated in situ on the substrate electrode surface via electrochemical deposition. These gold particles are uniformly distributed at the nanoscale, forming a three-dimensional island structure with excellent electronic conductivity and catalytic activity. The shell layer is a conductive polymer coating: bound to the periphery of the gold nanoparticles by electrostatic forces, forming a uniform and continuous conductive polymer film that completely encapsulates the gold nanoparticle core. The relationship between the gold nanoparticles and the conductive polymer is not a simple physical mixture or loose contact, but rather a stable chemically bonded interface formed by a carboxyl-containing linker (such as 3-mercaptopropionic acid). The thiol end specifically binds to the gold surface, while the carboxyl end attracts positively charged conductive polymer monomers to polymerize and grow in situ on its surface through electrostatic attraction, thus achieving a robust integrated structure of gold core and polymer shell.

[0036] In this embodiment, the gold nanoparticles and the conductive polymer are connected by a carboxyl-containing linker, which has a thiol group (-SH) at one end and a carboxyl group (-COOH) at the other end.

[0037] Furthermore, the linker is a carboxylated alkyl sulfide, preferably any one or more of 3-mercaptopropionic acid (3-MPA), mercaptooctanoic acid, or mercaptodecanoic acid.

[0038] The specific implementation process is as follows: First, the electrode with deposited gold nanoparticles is immersed in a 95% ethanol solution of 3-mercaptopropionic acid. Utilizing the specific strong chemisorption between the thiol groups and the gold surface (Au-S bond), a dense monolayer is formed on the surface of the gold nanoparticles through self-assembly. The terminal carboxyl groups of this self-assembled monolayer are exposed on the outside, serving as "anchor points" for the subsequent electrochemical polymerization of the conductive polymer. When the electrode is placed in an EDOT monomer solution and an oxidation potential is applied, the positively charged EDOT cationic free radicals or oligomers are electrostatically attracted by the negative charge of the carboxyl groups, preferentially nucleating and growing in the carboxyl-rich regions, ultimately forming a regular core-shell structure with gold nanoparticles as the core and a conductive polymer as the shell.

[0039] It is understandable that, through the specific chemical bonds of thiol-gold, the linker is arranged in a highly ordered manner on the surface of gold particles, avoiding the random adsorption of polymer chains. This ensures that the conductive polymer shell is uniformly and densely coated around each gold particle, forming a shell-core composite with regular morphology and controllable structure. The 3-MPA carbon chain has a moderate length (3 carbon atoms), which provides sufficient steric hindrance to prevent direct aggregation between gold particles, and ensures that the electron tunneling distance between the gold core and the polymer shell is short enough, which is conducive to the rapid transport of interfacial electrons. Homologues with longer carbon chains, such as mercaptooctanoic acid and mercaptodecanoic acid, can provide different spatial configurations and hydrophobic / hydrophilic balances, providing flexibility in material selection to adapt to different monomer polymerization systems. Moreover, the three have strong functional equivalence and can all achieve stable construction of the shell-core structure under the same preparation logic.

[0040] In this embodiment, the conductive polymer is any one of poly(3,4-ethylenedioxythiophene), polythiophene, or polypyrrole.

[0041] In this embodiment, the conductive polymer matrix material in the core-shell structure is limited to any one of poly(3,4-ethylenedioxythiophene) (PEDOT), polythiophene, or polypyrrole. All of the above conductive polymers are conductive polymers containing a conjugated π-bond system, possessing intrinsically high conductivity, good electrochemical activity, and biocompatibility.

[0042] It is understandable that the three conductive polymers mentioned above can all be generated by cationic radical polymerization of their respective monomers (EDOT, thiophene, and pyrrole) under electrochemical oxidation conditions. During the polymerization process, they all exhibit a positively charged doped state, enabling them to electrostatically recombine with the carboxyl-functionalized gold nanoparticle surface to form a core-shell structure. All three materials are hole-transporting conductive polymers with excellent electronic conductivity. When combined with gold nanoparticles, they can construct a highly efficient synergistic conductive network, ensuring that the inner sensing functional layer possesses highly sensitive signal transduction capabilities.

[0043] An anti-interference protective layer 130 is disposed on the outer surface of the composite sensing functional layer 120, and the anti-interference protective layer 130 is a poly(3-thiophene acetate) layer.

[0044] It is understood that this layer, located on the outermost side of the composite sensing functional layer, is an ultrathin, dense poly(3-acetylenol) organic film generated through electrochemical in-situ polymerization. The PTAA molecular chain has densely distributed carboxyl (-COOH) functional groups, which partially ionize in a neutral body fluid environment to form a negatively charged film layer. Simultaneously, its regular molecular arrangement forms microporous channels with specific sieving capabilities.

[0045] The electrochemical sensor for detecting dopamine with anti-interference provided in this application systematically solves all the core technical problems faced by existing sensors in complex living environments as pointed out in the background art through the synergistic effect of a three-layer structure: ① Addressing the issue of "low detection sensitivity"—signal enhancement effect The core-shell structure features a gold nanonucleus with excellent electronic conductivity, while the conductive polymer shell provides a high-specific-surface-area active reaction platform. The synergistic three-dimensional conductive network significantly increases the electrode's specific surface area compared to bare electrodes and traditional monolayer modified electrodes, resulting in an order-of-magnitude increase in the density of exposed active reaction sites. Furthermore, electrons released from the oxidation of dopamine on the conductive polymer shell surface are rapidly conducted through the highly conductive shell to the gold core "current collector," and then to the substrate electrode, forming an ultra-short and highly efficient electron transport path: "dopamine → conductive polymer shell → gold nanonucleus → substrate electrode." This synergistic conductivity mechanism greatly reduces interfacial charge transfer impedance, significantly amplifying the oxidation peak current density of dopamine and substantially improving detection sensitivity. This meets the high-sensitivity requirements for trace analysis in in vivo microenvironments (typically with dopamine concentrations in the nmol / L to μmol / L range).

[0046] ② Addressing the issues of "poor anti-interference specificity and low detection accuracy"—dual screening effect The outer PTAA protective layer establishes a dual-mode recognition mechanism of "charge repulsion + spatial size sieving": On the one hand, in a neutral body fluid environment (pH ≈ 7.4), ascorbic acid (pKa ≈ 4.2) and uric acid (pKa ≈ 5.4) exist in large quantities in anionic form, while the carboxyl negative charge carried by the PTAA layer generates a strong electrostatic repulsion effect on the above-mentioned negatively charged interfering substances, preventing them from penetrating the protective layer to reach the sensing interface and participate in the reaction; on the other hand, the size of the regular molecular channels of PTAA is precisely controlled within the range that can accommodate the passage of dopamine molecules (molecular weight 153 Da, diameter approximately 0.6–0.8 nm), while effectively blocking proteins (such as albumin, 66 kDa), polypeptides, and metabolic macromolecules with larger molecular sizes in biological body fluids. The synergistic effect of the above dual mechanisms enables the sensor to accurately identify and respond to the real dopamine signal even when the concentrations of ascorbic acid and uric acid are tens or even hundreds of times higher than those of dopamine. This significantly improves the signal-to-noise ratio and effectively solves the problem described in the background technology of "interference signals superimposed on the effective dopamine signal, severely masking the real signal," thus achieving accurate quantitative detection of dopamine in complex in vivo environments.

[0047] ③ Addressing the problem of "accumulation of oxidation products leading to electrode passivation and poor repeatability"—bidirectional diffusion mechanism The ultrathin, dense PTAA film not only allows dopamine molecules to diffuse inward to participate in electrochemical reactions, but its regular channels also support the timely and smooth outward diffusion of quinone intermediates generated in the reaction. This avoids the local accumulation of oxidation products at the electrode interface and the subsequent polymerization to form a non-conductive insulating film. This mechanism blocks the formation path of the electrode contamination layer at its source, resulting in a significant reduction in the response current decay rate during continuous scanning or long-term real-time monitoring, a stable detection baseline, and a significant reduction in the relative standard deviation (RSD) of the signal when the same electrode is reused. This greatly improves detection repeatability and data reliability, solving the problem described in the background art of "inability to accurately capture subtle metabolic abnormalities of dopamine in neurological diseases."

[0048] ④ Addressing the issues of "weak interfacial bonding, delamination of the modification layer, and short service life"—chemical bonding interfaces Unlike traditional physical adsorption methods such as drop coating and dip coating, this invention uses electrochemical deposition to grow gold nanoparticles in situ on the surface of the substrate electrode. A conductive polymer is firmly anchored to the gold core surface through thiol-gold chemical bonds and electrostatic assembly. The PTAA outer layer is covalently bonded to the sensing layer via electrochemical polymerization. The layers are bonded together by chemical bonds or strong electrostatic interactions, resulting in interfacial adhesion far superior to traditional physical coatings. This makes the electrode less prone to peeling, detachment, or cracking during long-term in vivo monitoring, significantly extending its service life and meeting the long-term stability requirements of in vivo dynamic monitoring.

[0049] Please see Figure 2 The flowchart below shows the steps of the preparation method of the anti-interference electrochemical sensor for dopamine detection provided in this application, including the following steps: S110: Provides a base electrode.

[0050] In this embodiment, a platinum electrode is selected as the detection substrate, which has the basic characteristics of excellent conductivity and strong electrochemical inertness, providing a basic carrier for the stable adhesion of multilayer functional films.

[0051] S120: A core-shell composite sensing functional layer is formed on the surface of the substrate electrode, the composite sensing functional layer comprising gold nanoparticles and a conductive polymer coated on the surface of the gold nanoparticles.

[0052] In this embodiment, the formation of the composite sensing functional layer includes: Gold nanoparticles were prepared on the surface of the substrate electrode using an electrochemical deposition method. Electrodes modified with gold nanoparticles were placed in a solution containing carboxyl alkane sulfides for self-assembly, thereby introducing carboxyl groups onto the surface of the gold nanoparticles. The self-assembled electrode was placed in a conductive polymer monomer solution for electrochemical polymerization, forming a conductive polymer coating layer on the surface of the gold nanoparticles, thus obtaining a core-shell structured composite sensing functional layer.

[0053] Furthermore, in the electrochemical deposition method, the deposition voltage is -0.1 V to -0.5 V, and the deposition time is 20 s to 60 s; preferably, the electrochemical deposition method is any one of constant potential electrodeposition, pulse electrodeposition, or cyclic voltammetric deposition. And / or, the self-assembly time is 12 h to 24 h; And / or, in the electrochemical polymerization, the polymerization voltage is 1.0 V to 1.5 V, and the polymerization time is 100 s to 400 s.

[0054] It should be noted that in this embodiment, the electrochemical deposition parameters (voltage -0.1V to -0.5V, time 20s to 60s) are within this potential range, and the tetrachloroaurate ions (AuCl4) - Gold atoms are controllably reduced to gold atoms, which then nucleate and grow into nanoscale particles on the electrode surface. The more negative the potential and the longer the time, the greater the amount of gold particles deposited and the slightly larger the particle size. Parameter tuning allows for precise control of the gold particle density and size, ensuring both high specific surface area active sites and preventing particle agglomeration or a decrease in specific surface area due to excessive growth. Pulsed electrodeposition and cyclic voltammetric deposition offer more flexible nucleation-growth control strategies; the former effectively suppresses the diffusion layer depletion effect, while the latter optimizes grain size distribution through repeated redox reactions, making it suitable for various equipment conditions.

[0055] It should be noted that the self-assembly time in this embodiment (12h–24h) ensures that 3-MPA molecules achieve saturated monolayer adsorption on the gold nanoparticle surface, forming an ordered, carboxyl-group-facing self-assembled monolayer. Too short a time will result in insufficient carboxyl group coverage, affecting the subsequent polymer binding amount and uniformity; too long a time will not provide additional gain. Thermodynamic equilibrium adsorption can be achieved within the 12–24h window, offering a wide process tolerance.

[0056] It should be noted that the electrochemical polymerization parameters provided in this embodiment are a voltage of 1.0V to 1.5V and a time of 100s to 400s. The polymerization voltage determines the driving force for monomer oxidation-induced polymerization. The 1.0 to 1.5V range is sufficient to initiate the electrochemical oxidation polymerization of EDOT (or thiophene, pyrrole) while avoiding solvent decomposition or polymer over-oxidation at excessively high potentials. The polymerization time is the core parameter for controlling the shell thickness: the longer the time, the more conductive polymer is deposited, and the thicker the shell. The adjustable range of 100 to 400s allows for customization of the optimal film thickness according to different detection requirements—a thinner film layer is beneficial for rapid response and electron transfer (emphasizing sensitivity), while a thicker film layer can provide higher stability and mechanical strength (emphasizing durability). This flexible and adjustable parameter characteristic enables the present invention to adapt to different application scenarios, fully demonstrating the precise controllability of the preparation process.

[0057] The process windows for the above parameter combinations have all been rigorously verified through experiments. Sensor functional films prepared within this range exhibit uniform and stable growth, high reproducibility of electrode performance, and small batch-to-batch differences, thus solving the engineering bottleneck of "large batch-to-batch differences in manual drop coating" mentioned in the background technology.

[0058] S130: A poly(3-thiophene acetate) anti-interference protective layer is formed on the outer surface of the composite sensing functional layer.

[0059] In this embodiment, the formation of the poly(3-thiophene acetate) anti-interference protective layer includes: placing the electrode with the composite sensing functional layer in a 3-thiophene acetate solution, and forming the poly(3-thiophene acetate) anti-interference protective layer on the outer surface of the composite sensing functional layer by electrochemical polymerization.

[0060] It is understandable that an electrode with a composite sensing functional layer is placed in a 3-thiophene acetate (TAA) solution, and an electrochemical polymerization method is used to form a poly(3-thiophene acetate) (PTAA) anti-interference protective layer on the outer surface of the composite sensing functional layer. Specifically, a mixed solvent system of boron trifluoride diethyl ether: trifluoroacetic acid = 3:1 is prepared, and 0.05 mol / L of TAA monomer is dissolved in it. The electrode is immersed in this solution, and an appropriate oxidation potential is applied to allow the TAA monomer to polymerize in situ on the outer surface of the electrode to form a PTAA film.

[0061] It is understandable that the PTAA film generated by electrochemical polymerization grows uniformly outward from the electrode surface, unlike the uneven thickness, edge accumulation, or pinhole defects that may occur with drop casting. This ensures that the protective layer has complete and dense coverage, eliminating the possibility of interfering substances "short-circuiting" to the sensing interface through defect sites. The thickness of the PTAA layer can be precisely and digitally controlled by the polymerization charge (i.e., the integrated charge), with minimal thickness deviation between different batches, ensuring batch-to-batch consistency in anti-interference performance. Under electrochemical polymerization conditions, TAA monomers form a conjugated polymer backbone through α-α coupling of thiophene rings, while the carboxyl groups are fully retained as side-chain functional groups, ensuring that the PTAA layer has sufficient negative charge density to perform electrostatic repulsion. The slow, controlled growth mode of electrochemical polymerization is conducive to the orderly stacking of polymer chains, forming molecular-level channels of uniform size, providing a structural basis for spatial size sieving function. This step is completed continuously with the electrochemical preparation of the core-shell sensing layer in the same equipment system, eliminating the need to transfer the electrode to other film-forming equipment, simplifying the process and reducing the risk of contamination and errors introduced by operational steps.

[0062] Furthermore, before forming the composite sensing functional layer, the substrate electrode is pretreated: the substrate electrode is subjected to oxygen plasma treatment, and then cyclic voltammetry is performed in an acid solution until the curve stabilizes, in order to purify and activate the electrode surface.

[0063] It is understood that this embodiment employs oxygen plasma treatment, which effectively removes residual organic contaminants, oil stains, and adsorbed impurities from the electrode surface through high-energy particle bombardment. Simultaneously, it introduces oxygen-containing polar functional groups (such as -OH and -C=O) into the surface, significantly enhancing the hydrophilicity and surface energy of the electrode surface. This provides a uniform and highly active nucleation interface for the subsequent electrochemical deposition of gold nanoparticles in the solution phase. Cyclic voltammetry using sulfuric acid effectively removes unstable oxide layers and adsorbed impurities formed on the platinum (or other electrode materials) surface during storage through repeated redox processes within the potential range of -0.2 V to 1.5 V. A stable scan curve indicates that the electrode surface has reached an electrochemically "clean" and "activated" state, with a reduced and stable background current. The electrode surface, after dual activation treatment by both physical and chemical methods, possesses a high density of active sites (such as step sites and edge sites on the platinum surface), providing ample high-energy binding sites for the electrochemical nucleation of gold nanoparticles. The bonding force between the gold particles and the substrate is significantly enhanced, ensuring the long-term adhesion of subsequent multilayer functional films from the bottom layer.

[0064] Furthermore, after forming the poly(3-acetylthiophene) anti-interference protective layer, an activation process is also included: the obtained electrode is activated by cyclic voltammetry scanning in a buffer solution until the electrochemical response curve is stable.

[0065] It is understandable that unpolymerized monomer molecules, oligomers, doped counterions, and solvent molecules may remain inside the functional film during electrochemical polymerization. Activation treatment, through repeated potential scans, allows these unstable components to be released from the film and diffuse into the solution, while simultaneously releasing the internal stress generated during film growth, bringing the film structure towards a stable configuration with the lowest energy. Newly prepared polymer films may contain some peroxide groups or uncapped active chain ends, which may cause non-specific adsorption or drift signals in subsequent detection. Multi-turn CV scans, through a gentle electrochemical redox process, transform these unstable groups into stable forms, minimizing and maintaining a constant background current of the electrode. After activation treatment, the electrode exhibits a stable electrochemical response curve and a flat baseline, indicating that the electrode has reached a stable state after electrochemical "aging." After different electrodes are treated with a uniform activation procedure, their initial response states tend to be consistent, effectively eliminating individual differences that may arise during the preparation process, and is a key step in ensuring batch-to-batch repeatability.

[0066] The present invention provides a method for fabricating an anti-interference electrochemical sensor for dopamine detection. By constructing a gold-doped conductive polymer composite sensing functional layer on the surface of an electrode substrate, the synergistic electrochemical effect between gold nanoparticles and the conductive polymer effectively optimizes the microstructure of the electrode interface, accelerates the interfacial electron transfer rate, significantly enhances the sensor's electrochemical response to dopamine, and substantially improves the structural stability, detection repeatability, and electrode lifespan of the sensing interface. Furthermore, the present invention introduces a poly(3-acetylthiophene) functional modification layer as a specific anti-interference interface. Utilizing its unique spatial sieving effect and charge-selective repulsion characteristics, it can efficiently shield coexisting non-target electroactive interfering molecules such as ascorbic acid and uric acid in biological matrices. Simultaneously, it significantly improves the electrode's resistance to bioadsorption and passivation, effectively solving the technical challenges of low detection accuracy and poor anti-interference performance of dopamine in complex living biological environments. This invention employs a layered composite modification strategy to construct an integrated multifunctional sensing interface, which balances high detection sensitivity, excellent anti-interference performance, and detection stability. It enables real-time, in-situ, and accurate detection of dopamine in complex biological samples and in vivo environments, making it suitable for practical applications in the study of neurological disease mechanisms and clinical auxiliary detection.

[0067] The electrochemical sensor for detecting dopamine with resistance to interference provided in this application, or the electrochemical sensor for detecting dopamine with resistance to interference prepared according to the preparation method described herein, is used in at least one of the following (a) to (d): (a) Preparation of detection products for detecting dopamine in complex biological samples—such as cerebrospinal fluid, serum, brain tissue homogenate, and other ex vivo samples, as well as in vivo detection; (b) Prepare detection products for detecting catecholamines—including neurotransmitters with a catechol structure such as serotonin, norepinephrine, and epinephrine; (c) Develop products for dynamic monitoring of pathological models of Parkinson's disease and / or depression—for real-time dynamic monitoring of dopamine release in cell models and animal models; (d) Prepare detection products for the detection of dopamine or phenolic substances in the environment or food—for rapid screening of trace dopamine residues and similar phenolic substances in water and food samples.

[0068] This invention is based on a dual-layer composite interface design consisting of a "highly conductive core-shell sensing inner layer + a poly(3-acetylacetonate) electrostatic sieving anti-interference outer layer". The constructed sensor is not only suitable for dopamine detection in standard solution systems, but also exhibits wide applicability in the following complex scenarios due to its unique multiple anti-interference and anti-contamination mechanisms: Applications (a) Detection of complex biological samples: The PTAA outer layer effectively blocks high concentrations of proteins, peptides, and metabolic impurities in biological fluids, allowing the sensor to directly detect dopamine levels in cerebrospinal fluid, serum, and brain tissue homogenates without cumbersome sample pretreatment (such as protein precipitation and solid-phase extraction), and the detection results are accurate and reliable. This characteristic makes it suitable for both batch precision detection of ex vivo samples and real-time, in-situ tracking of dopamine release in in vivo brain regions, providing neuroscience research with an integrated tool that combines in vitro and in vivo detection capabilities.

[0069] Application (b) Detection of catecholamines: The electrostatic repulsion screening mechanism of the PTAA layer provides universal shielding against negatively charged interfering substances (such as AA and UA), while maintaining permeability to positively or neutrally charged small-molecule catechols (such as norepinephrine and epinephrine). Therefore, this sensor can be extended to the highly specific detection of various catecholamine neurotransmitters, providing a flexible technical platform for the simultaneous analysis of neurotransmitters in various neurological diseases (such as depression, anxiety, pheochromocytoma, etc.).

[0070] Application (c) Dynamic monitoring of pathological models: The sensor's excellent resistance to passivation and long-term stability make it suitable for long-term dynamic monitoring of dopamine release in Parkinson's disease, depression-related cell models, and animal models. Researchers can use this sensor to track changes in dopamine release in disease models at different stages of development or before and after drug intervention in real time, providing direct electrochemical evidence for elucidating pathological mechanisms, identifying drug targets, and evaluating efficacy. It is an important tool for neuropharmacology and disease mechanism research.

[0071] Application (d) Environmental and Food Trace Detection: The sensor's high sensitivity to dopamine and phenolic substances, along with its strong robustness against matrix interference, allows for further expansion into the rapid screening of trace dopamine residues and phenolic contaminants in drinking water, surface water, and processed food samples. Compared to traditional chromatography-mass spectrometry methods, this sensor is simple to operate, has a fast detection speed, and low instrument cost, making it a promising candidate for rapid on-site detection.

[0072] In summary, the application scenarios of this invention extend from basic medical research to clinical auxiliary diagnosis, and from biological samples to environmental and food detection, fully demonstrating its technical value and wide applicability as a high-performance electrochemical sensing platform.

[0073] The technical solutions described above in this application will be explained in detail below with reference to specific embodiments.

[0074] Example 1 (1) Platinum electrodes were selected as the detection substrate, which have the basic characteristics of excellent conductivity and strong electrochemical inertness, providing a basic carrier for the stable adhesion of multilayer functional films. First, the electrode substrate was treated with oxygen plasma for 180s, and then cyclic voltammetry was performed on the electrode in 0.5 mol / L sulfuric acid solution. The scanning voltage range was -0.2V to 1.5V, and the scanning was continued until the cyclic voltammetry curve stabilized, so as to purify and activate the surface of the platinum electrode, remove surface contaminants and unstable oxide films, reduce the background signal of the substrate, and optimize the bonding performance of the material modification interface.

[0075] (2) By electrochemical deposition, the electrode was placed in a solution of 0.01 mol / L tetrachloroauric acid (HAuCl4) and 0.1 mol / L perchloric acid (HClO4) and a voltage of -0.5 V was applied for 45 s to generate gold nanoparticles on the electrode surface. Then, the gold-modified electrode was immersed in a 95% ethanol solution of 5 mmol / L 3-mercaptopropionic acid (3-MPA) to perform self-assembly. Carboxyl groups were introduced at the interface of the gold nanoparticles by utilizing the specific binding effect of thiol groups and gold. Finally, the electrode was placed in a 10 mmol / L solution of 3,4-ethylenedioxythiophene (EDOT) without ion coexistence. The reference electrode was used in a double salt bridge manner, and a voltage of 1.3 V was applied for 300 s. The positively charged conductive polymer was connected by electrostatic interaction. A core-shell structure conductive polymer-gold nanoparticle sensing layer was formed on the surface of the modified electrode, rather than a simple physical drop-coating. This structure significantly increases the specific surface area, thereby increasing the number of active reaction sites for the electrochemical oxidation of dopamine. Simultaneously, the gold nanoparticles possess excellent electronic conductivity, enabling them to form synergistic conductive pathways with conductive polymers, greatly accelerating the electron transfer rate at the electrode interface. Furthermore, compared to traditional surface modifications, the gold-doped structure significantly enhances the bonding strength between the functional layer and the substrate, resolving issues such as modification layer detachment and interface peeling, and improving electrode lifespan and detection repeatability.

[0076] (3) The electrode with the above-mentioned sensing layer was placed in a 0.05 mol / L solution of 3-thiophene acetate (TAA) in boron trifluoride diethyl ether: trifluoroacetic acid (3:1) for electrochemical polymerization, and finally PTAA was formed as the outermost anti-interference layer. This functional layer relies on the carboxyl functional group and regular molecular channel structure of poly(3-thiophene acetate) molecules to achieve the dual anti-interference technology effect: First, charge repulsion screening. In the physiological environment, ascorbic acid, uric acid and other interfering molecules are negatively charged in the neutral body fluid environment. The poly(3-thiophene acetate) modified interface can block the negatively charged interfering molecules from contacting the sensing active interface through electrostatic repulsion; Second, spatial size screening. The micropore size of the dense film formed by 3-thiophene acetate is adapted to the penetration of dopamine small molecules, which allows the target dopamine molecules to penetrate smoothly and undergo electrochemical reaction, while blocking the adsorption of large molecular biological proteins and metabolic impurities on the electrode surface, thus achieving the effect of anti-biological passivation and anti-electrode contamination. At the same time, the thin film can enable rapid bidirectional diffusion of oxidation products, and the quinone intermediates generated by dopamine oxidation can penetrate the film layer in time, preventing the oxidation products from continuously accumulating and passivating the electrode.

[0077] (4) The double-layer composite modified electrode is gently rinsed with ultrapure water to remove unpolymerized monomers and residual electrolyte on the surface. Then, it is activated by multiple cycles of cyclic voltammetry scanning in a blank buffer solution until the electrochemical response curve is stable and the baseline is stable, eliminating residual stress and unstable groups on the surface during the preparation process, so that the electrochemical performance of the electrode reaches a steady state.

[0078] (5) The activated sensor electrode is air-dried naturally and stored in a dry place away from light to obtain a dopamine electrochemical detection sensor with high sensitivity, high stability and strong anti-interference performance.

[0079] Furthermore, this invention employs an electrochemical polymerization process to functionally modify the electrode. The pretreated electrode is placed in a mixed solution of boron trifluoride diethyl ether / trifluoroacetic acid (volume ratio 3:1) containing 0.05 mol / L thiophene 3-acetate (TAA) to carry out electrochemical polymerization, successfully preparing a poly(3-acetylthiophene) (PTAA) modified electrode. To verify the anti-interference performance and specific recognition ability of the PTAA functional layer, this invention conducts multi-system electrochemical comparative tests. The test systems include 0.1 mol / L phosphate buffered saline (PBS), a single solution of 1 mmol / L dopamine (DA), a mixed solution of 1 mmol / L ascorbic acid (AA) and 1 mmol / L uric acid (UA), and a multi-component mixed solution where the concentrations of DA, AA, and UA are all 1 mmol / L. Electrochemical signals of each system are acquired and analyzed using cyclic voltammetry.

[0080] Figure 3The cyclic voltammetric curves of the PTAA-modified electrode in different test solutions are shown. The test results indicate that the PTAA-modified electrode showed no obvious redox characteristic peaks in blank PBS buffer and a mixed solution of AA and UA, indicating that the PTAA interface is almost unresponsive to the two common electroactive interfering substances, AA and UA, at these concentrations. However, a pair of significant and characteristic asymmetric redox peaks were observed in pure DA solution, demonstrating that the PTAA-modified electrode possesses excellent electrochemical response to dopamine. Further testing in a complex mixed system of DA, AA, and UA showed that the coexistence of AA and UA had almost no inhibitory or superimposed interference effect on the DA redox signal, and the electrode could still stably output the characteristic dopamine response signal. These results fully demonstrate that the PTAA functional modification layer prepared in this invention can effectively shield the electrochemical interference of AA and UA, exhibiting excellent specificity and anti-interference performance for dopamine detection.

[0081] To verify the dopamine detection performance of the sensor of this invention, a bare electrode and a single PTAA-modified electrode were set up as control groups in this experiment. The bare electrode, the single PTAA-modified electrode, and the composite sensor of this invention were respectively placed in a 1 mmol / L dopamine (DA) solution for electrochemical detection, and the corresponding cyclic voltammetry tests were performed. Figure 4 The figures show cyclic voltammetry results for different electrodes in dopamine solution. The results indicate that asymmetric redox characteristic peaks corresponding to dopamine were observed in all three electrode groups. The PTAA-modified interface exhibits a strong electrostatic interaction with dopamine molecules, resulting in a significantly better electrochemical response signal to dopamine from the single PTAA-modified electrode compared to the bare electrode. The composite sensor prepared in this invention demonstrates optimal dopamine detection performance. This is attributed to the core-shell structure of the composite sensing layer, which effectively optimizes the electrode interface microstructure, increases electrochemical active sites, and significantly accelerates the interface electron transfer rate, synergistically enhancing the sensor's dopamine detection response capability. This fully verifies the significant advantage of the composite structure in improving detection sensitivity.

[0082] To further verify the electrochemical stability and anti-passivation performance of the sensor of the present invention during dopamine detection, the dopamine sensor prepared in this invention was placed in a 1 mmol / L dopamine solution and subjected to 20 consecutive cycles of cyclic voltammetry scanning. The test results are as follows: Figure 5 As shown in the figure, experimental data shows that the peak current of dopamine oxidation in the first cycle was 537.7 nA, and after 20 consecutive scans, the peak current of oxidation was 497.5 nA. After multiple rounds of continuous electrochemical reactions, the sensor oxidation signal only decreased by 7.5%. This result indicates that the dopamine sensor of the present invention exhibits small fluctuations in electrochemical signal and excellent response stability during continuous dopamine detection. It can effectively resist the interface passivation effect caused by the accumulation of dopamine oxidation products and has good long-term cyclic detection stability.

[0083] Therefore, the dopamine electrochemical sensor provided by this invention can be used for real-time monitoring of dopamine. 1) A core-shell structure conductive polymer-gold nanoparticle sensing layer is constructed, which significantly increases the electrochemical active sites of the electrode, accelerates interfacial electron transfer, and significantly enhances the dopamine electrochemical response current. 2) Simultaneously, a dense poly(3-acetylthiophene) film is prepared through in-situ polymerization. Relying on the carboxyl charge characteristics, an electrostatic repulsion mechanism is constructed, which can effectively block negatively charged interference molecules from contacting the electrode interface with biological proteins, while not hindering the electrochemical reaction of small dopamine molecules. This solves the core problems of traditional sensors, such as weak anti-interference ability, easy passivation, and low detection accuracy, and is suitable for detection scenarios in living organisms and complex biological matrices. 3) This invention adopts a standardized electrochemical in-situ polymerization process, with precise and controllable preparation parameters, uniform and stable growth of functional films, high reproducibility of electrode performance, small batch-to-batch differences, and stable batch preparation, possessing excellent prospects for scientific research promotion and industrial application.

[0084] The above are merely preferred embodiments of this application, and only specifically describe the technical principles of this application. These descriptions are only for explaining the principles of this application and should not be construed as limiting the scope of protection of this application in any way. Based on this explanation, any modifications, equivalent substitutions, and improvements made within the spirit and principles of this application, as well as other specific embodiments of this application that can be conceived by those skilled in the art without creative effort, should be included within the scope of protection of this application.

Claims

1. An electrochemical sensor for detecting dopamine with anti-interference capability, characterized in that, include: Base electrode; A composite sensing functional layer is disposed on the surface of the substrate electrode. The composite sensing functional layer has a core-shell structure, which includes gold nanoparticles and a conductive polymer coated on the surface of the gold nanoparticles. An anti-interference protective layer is disposed on the outer surface of the composite sensing functional layer, and the anti-interference protective layer is a poly(3-thiophene acetate) layer.

2. The electrochemical sensor for detecting dopamine with anti-interference capability according to claim 1, characterized in that, The gold nanoparticles and the conductive polymer are connected by a carboxyl-containing linker. One end of the linker is bound to the gold nanoparticles via a thiol group, and the other end of the linker is bound to the conductive polymer via a carboxyl group.

3. The electrochemical sensor for detecting dopamine with anti-interference capability according to claim 2, characterized in that, The linker is a carboxylated alkyl sulfide, preferably any one or more of 3-mercaptopropionic acid, mercaptooctanoic acid, or mercaptodecanoic acid.

4. The electrochemical sensor for detecting dopamine with anti-interference capability according to claim 1, characterized in that, The conductive polymer is any one of poly(3,4-ethylenedioxythiophene), polythiophene, or polypyrrole.

5. The electrochemical sensor for detecting dopamine with anti-interference capability according to claim 1, characterized in that, The base electrode is any one of a platinum electrode, a gold electrode, or a carbon-based electrode.

6. A method for preparing an electrochemical sensor for detecting dopamine with anti-interference capability as described in any one of claims 1 to 5, characterized in that, Includes the following steps: Provide a base electrode; A core-shell composite sensing functional layer is formed on the surface of the substrate electrode. The composite sensing functional layer includes gold nanoparticles and a conductive polymer coated on the surface of the gold nanoparticles. A poly(3-thiophene acetate) anti-interference protective layer is formed on the outer surface of the composite sensing functional layer.

7. The preparation method according to claim 6, characterized in that, The formation of the composite sensing functional layer includes: Gold nanoparticles were prepared on the surface of the substrate electrode using an electrochemical deposition method. Electrodes modified with gold nanoparticles were placed in a solution containing carboxyl alkane sulfides for self-assembly, thereby introducing carboxyl groups onto the surface of the gold nanoparticles. The self-assembled electrode was placed in a conductive polymer monomer solution for electrochemical polymerization, forming a conductive polymer coating layer on the surface of the gold nanoparticles, thus obtaining a core-shell structured composite sensing functional layer.

8. The preparation method according to claim 7, characterized in that: In the electrochemical deposition method, the deposition voltage is -0.1 V to -0.5 V, and the deposition time is 20 s to 60 s; preferably, the electrochemical deposition method is any one of constant potential electrodeposition, pulse electrodeposition, or cyclic voltammetric deposition. And / or, the self-assembly time is 12 h to 24 h; And / or, in the electrochemical polymerization, the polymerization voltage is 1.0 V to 1.5 V, and the polymerization time is 100 s to 400 s.

9. The preparation method according to claim 6, characterized in that, The formation of the poly(3-thiophene acetate) anti-interference protective layer includes: placing the electrode with the composite sensing functional layer in a 3-thiophene acetate solution, and forming the poly(3-thiophene acetate) anti-interference protective layer on the outer surface of the composite sensing functional layer by electrochemical polymerization.

10. The preparation method according to claim 6, characterized in that, Before forming the composite sensing functional layer, the substrate electrode is pretreated by oxygen plasma treatment and then cyclic voltammetry is performed in an acid solution until the curve stabilizes, in order to purify and activate the electrode surface.

11. The preparation method according to claim 6, characterized in that, After forming the poly(3-acetylthiophene) anti-interference protective layer, an activation process is also included: the resulting electrode is activated by cyclic voltammetry scanning in a buffer solution until the electrochemical response curve is stable.

12. The use of the electrochemical sensor for detecting dopamine against interference according to any one of claims 1 to 5, or the electrochemical sensor for detecting dopamine against interference prepared by the preparation method according to any one of claims 6 to 11, in at least one of the following (a) to (d): (a) Preparation of a detection product for detecting dopamine in complex biological samples; (b) Prepare detection products for detecting catecholamines; (c) Develop products for dynamic monitoring of pathological models of Parkinson's disease and / or depression; (d) Prepare detection products for the detection of dopamine or phenolic substances in the environment or food.

Images