Boosted Sensitivity of Single-Atom Sites for Dopamine and Hydrogen Peroxide Detection

Abstract

Single-atom (SA) sites have garnered significant attention in electrochemical applications due to their ability to leverage the unique electronic properties of isolated metal atoms, thereby enhancing interfacial charge transfer and detection sensitivity. Despite the limited exploration of electrochemical sensors utilizing SA, their integration into sensing electrodes holds great promise for improving the sensitivity and selectivity of bioactive molecule detection. In this study, SA modified electrodes were developed by anchoring transition metal atoms (Fe, Co, or Cu) onto nitrogen-doped graphene (N–C) via M–N–C coordination, synthesized through a ball milling–pyrolysis method. Electrochemical impedance spectroscopy measurements demonstrated a significant reduction in electrochemical impedance for Fe, Co, and Cu SA electrodes, indicating an enhanced electron transfer rate at the sensor interface. To evaluate the electrochemical sensing performance of SA-modified electrodes, dopamine (DA) and hydrogen peroxide (H₂O₂)—two biologically important molecules—were selected as representative analytes. Chronoamperometry revealed that Fe SA exhibited an enhanced sensitivity toward DA, reaching 0.02 A/µM, attributed to the unique electronic structure and catalytic properties of Fe sites, whereas Co SA and Cu SA did not show a notable improvement in DA detection sensitivity compared to the N–C electrode (0.01 A/µM). In contrast, Fe, Co, and Cu SA electrodes demonstrated improved sensitivity for H₂O₂ detection, achieving 0.35, 0.28, and 0.35 A/mM, respectively, surpassing the performance of the N–C electrode (0.076 A/mM). Density functional theory calculations of DA oxidation kinetics demonstrated that Fe–N site facilitated the adsorption and conversion of OH, thereby improving electrochemical response. These findings highlight the potential of SA as an effective electrode modification strategy for advancing electrochemical sensing technologies and enabling highly sensitive biomolecular detection.

Keywords

dopamine and hydrogen peroxide detection / electrochemical sensors / single-atom sites

References

[1] K. M. Costa and G. Schoenbaum, “Dopamine,” Current Biology 32, no. 15 (2022): R817–R824.

[2] C. Liu, X. Lin, J. Liao, et al., “Carbon Dots-Based Dopamine Sensors: Recent Advances and Challenges,” Chinese Chemical Letters 35, no. 12 (2024): 109598.

[3] C. Bucolo, G. M. Leggio, F. Drago, and S. Salomone, “Dopamine Outside the Brain: The Eye, Cardiovascular System and Endocrine Pancreas,” Pharmacology & Therapeutics 203 (2019): 107392.

[4] A. H. V. Schapira, “Dopamine Agonists and Neuroprotection in Parkinson's Disease,” European Journal of Neurology 9, no. s3 (2002): 7–14.

[5] F. Antunes and P. M. Brito, “Quantitative Biology of Hydrogen Peroxide Signaling,” Redox Biology 13 (2017): 1–7.

[6] J. Bai and X. Jiang, “A Facile One-Pot Synthesis of Copper Sulfide-Decorated Reduced Graphene Oxide Composites for Enhanced Detecting of H₂O₂ in Biological Environments,” Analytical Chemistry 85, no. 17 (2013): 8095–8101.

[7] J. D. Lambeth, “NOX Enzymes and the Biology of Reactive Oxygen,” Nature Reviews Immunology 4, no. 3 (2004): 181–189.

[8] W. Chen, S. Cai, Q.-Q. Ren, W. Wen, and Y.-D. Zhao, “Recent Advances in Electrochemical Sensing for Hydrogen Peroxide: A Review,” Analyst 137, no. 1 (2012): 49–58.

[9] C. de Gracia Lux, S. Joshi-Barr, T. Nguyen, et al., “Biocompatible Polymeric Nanoparticles Degrade and Release Cargo in Response to Biologically Relevant Levels of Hydrogen Peroxide,” Journal of the American Chemical Society 134, no. 38 (2012): 15758–15764.

[10] H. Song, H. Zhao, X. Zhang, et al., “3D Hierarchical Hollow Hydrangea-Like Fe3+@ɛ-MnO₂ Microspheres With Excellent Electrochemical Performance for Dopamine and Hydrogen Peroxide,” Biosensors and Bioelectronics 133 (2019): 250–257.

[11] R. Sha, N. Vishnu, and S. Badhulika, “Bimetallic Pt-Pd Nanostructures Supported on MoS₂ as an Ultra-High Performance Electrocatalyst for Methanol Oxidation and Nonenzymatic Determination of Hydrogen Peroxide,” Microchimica Acta 185, no. 8 (2018): 399.

[12] Z. Tian, X. Qin, F. Shao, et al., “Electrofluorochromic Imaging Analysis of Dopamine Release From Living PC12 Cells With Bipolar Nanoelectrodes Array,” Chinese Chemical Letters 34, no. 1 (2023): 107656.

[13] J. Li, A. Reimers, K. M. Dang, et al., “3D Printed Neural Tissues With In Situ Optical Dopamine Sensors,” Biosensors and Bioelectronics 222 (2023): 114942.

[14] Q. Huang, H. Zhang, S. Hu, et al., “A Sensitive and Reliable Dopamine Biosensor Was Developed Based on the Au@Carbon Dots–Chitosan Composite Film,” Biosensors and Bioelectronics 52 (2014): 277–280.

[15] M. U. Nisa, A. Yaqub, M. H. Khan, et al., “Nanotechnology-Driven Electrochemical Neurotransmitter Sensing as a Fundamental Approach Towards Improving Diagnostics and Therapeutics: A Review,” Sensors and Actuators Reports 9 (2025): 100292.

[16] H. Su, F. Sun, Z. Lu, J. Zhang, W. Zhang, and J. Liu, “A Wearable Sensing System Based on Smartphone and Diaper to Detect Urine In-Situ for Patients With Urinary Incontinence,” Sensors and Actuators B: Chemical 357 (2022): 131459.

[17] Y. Yang, H. Dong, H. Yin, et al., “Fabrication of Nonenzymatic Electrochemical Interface for Ratiometric and Simultaneous Detection of Hydrogen Peroxide, Dopamine, and Ascorbic Acid,” Microchemical Journal 178 (2022): 107344.

[18] M. Devendiran, K. Krishna Kumar, and S. Sriman Narayanan, “Fabrication of a Novel Ferrocene/Thionin Bimediator Modified Electrode for the Electrochemical Determination of Dopamine and Hydrogen Peroxide,” Journal of Electroanalytical Chemistry 802 (2017): 78–88.

[19] M. Meyyappan, “Nano Biosensors for Neurochemical Monitoring,” Nano Convergence 2, no. 1 (2015): 18.

[20] H. Kaur, S. S. Siwal, R. V. Saini, N. Singh, and V. K. Thakur, “Significance of an Electrochemical Sensor and Nanocomposites: Toward the Electrocatalytic Detection of Neurotransmitters and Their Importance Within the Physiological System,” ACS Nanoscience Au 3, no. 1 (2023): 1–27.

[21] Z. Liu, B. Zhao, Y. Shi, C. Guo, H. Yang, and Z. Li, “Novel Nonenzymatic Hydrogen Peroxide Sensor Based on Iron Oxide–Silver Hybrid Submicrospheres,” Talanta 81, no. 4 (2010): 1650–1654.

[22] W. He, J. Wu, J. Liu, and J. Li, “Single-Atom Nanozymes for Catalytic Therapy: Recent Advances and Challenges,” Advanced Functional Materials 34, no. 16 (2024): 2312116.

[23] B. Jiang and M. Liang, “Advances in Single-Atom Nanozymes Research,” Chinese Journal of Chemistry 39, no. 1 (2021): 174–180.

[24] H. Xiang, W. Feng, and Y. Chen, “Single-Atom Catalysts in Catalytic Biomedicine,” Advanced Materials 32, no. 8 (2020): 1905994.

[25] S. Ji, Y. Wang, H. Liu, et al., “Regulating the Electronic Synergy of Asymmetric Atomic Fe Sites With Adjacent Defects for Boosting Activity and Durability Toward Oxygen Reduction,” Advanced Functional Materials 34, no. 29 (2024): 2314621.

[26] S. Ji, Y. Mou, H. Liu, et al., “Manipulating the Electronic Properties of an Fe Single Atom Catalyst via Secondary Coordination Sphere Engineering to Provide Enhanced Oxygen Electrocatalytic Activity in Zinc-Air Batteries,” Advanced Materials 36, no. 44 (2024): 2410121.

[27] C. Li, O. J. H. Chai, Q. Yao, et al., “Electrocatalysis of Gold-Based Nanoparticles and Nanoclusters,” Materials Horizons 8, no. 6 (2021): 1657–1682.

[28] X. Xie, D. P. Wang, C. Guo, et al., “Single-Atom Ruthenium Biomimetic Enzyme for Simultaneous Electrochemical Detection of Dopamine and Uric Acid,” Analytical Chemistry 93, no. 11 (2021): 4916–4923.

[29] X. Zhang, G. Li, G. Chen, D. Wu, X. Zhou, and Y. Wu, “Single-Atom Nanozymes: A Rising Star for Biosensing and Biomedicine,” Coordination Chemistry Reviews 418 (2020): 213376.

[30] Z. Shen, Y. Yu, Z. Zhao, et al., “N, O Trans-Coordinating Silver Single-Atom Catalyst for Robust and Efficient Ammonia Electrosynthesis From Nitrate,” Applied Catalysis, B: Environmental 331 (2023): 122687.

[31] J. Zhao, Y. Guo, Z. Zhang, et al., “Out-of-Plane Coordination of Iridium Single Atoms With Organic Molecules and Cobalt–Iron Hydroxides to Boost Oxygen Evolution Reaction,” Nature Nanotechnology 20, no. 1 (2025): 57–66.

[32] K. He, Z. Huang, C. Chen, C. Qiu, Y. L. Zhong, and Q. Zhang, “Exploring the Roles of Single Atom in Hydrogen Peroxide Photosynthesis,” Nano-Micro Letters 16, no. 1 (2023): 23.

[33] S. A. Hira, M. Nallal, K. Rajendran, et al., “Ultrasensitive Detection of Hydrogen Peroxide and Dopamine Using Copolymer-Grafted Metal-Organic Framework Based Electrochemical Sensor,” Analytica Chimica Acta 1118 (2020): 26–35.

[34] Y. Lei, D. Butler, M. C. Lucking, et al., “Single-Atom Doping of MoS₂ With Manganese Enables Ultrasensitive Detection of Dopamine: Experimental and Computational Approach,” Science Advances 6, no. 32 (2020): eabc4250.

[35] Y. Liang, P. Zhao, J. Zheng, et al., “Fe Single-Atom Electrochemical Sensors for H₂O₂ Produced by Living Cells,” ACS Applied Nano Materials 5, no. 8 (2022): 11852–11863.

[36] R. Li, W. Guo, Z. Zhu, et al., “Single-Atom Indium Boosts Electrochemical Dopamine Sensing,” Analytical Chemistry 95, no. 18 (2023): 7195–7201.

[37] Z. Yang, Y. Kong, and C. Qi, “Regulation of the Coordination Number of Zn Single Atoms to Boost Electrochemical Sensing of H₂O₂,” Nanoscale 17, no. 2 (2025): 1069–1079.

[38] Y. Liu, P. Zhao, Y. Liang, et al., “Single-Atom Nanozymes Co–N–C as an Electrochemical Sensor for Detection of Bioactive Molecules,” Talanta 254 (2023): 124171.

[39] J.-L. Yang, P. Yang, D.-Q. Cai, Z. Wang, and H. J. Fan, “Atomically Dispersed Fe–N4 and Ni–N4 Independent Sites Enable Bidirectional Sulfur Redox Electrocatalysis,” Nano Letters 23, no. 9 (2023): 4000–4007.

[40] J. Zhong, Z. Liang, N. Liu, et al., “Engineering Symmetry-Breaking Centers and d-Orbital Modulation in Triatomic Catalysts for Zinc-Air Batteries,” ACS Nano 18, no. 7 (2024): 5258–5269.

[41] Z. Hsine, R. Mlika, N. Jaffrezic-Renault, and H. Korri-Youssoufi, “Review—Recent Progress in Graphene Based Modified Electrodes for Electrochemical Detection of Dopamine,” Chemosensors [Online] 10, no. 7 (2022): 249.

[42] D. Grieshaber, R. MacKenzie, J. Vörös, and E. Reimhult, “Electrochemical Biosensors – Sensor Principles and Architectures,” Sensors 8 (2008): 1400–1458.

[43] W. Sun, X. Li, Y. Wang, R. Zhao, and K. Jiao, “Electrochemistry and Electrocatalysis of Hemoglobin on Multi-Walled Carbon Nanotubes Modified Carbon Ionic Liquid Electrode With Hydrophilic EMIMBF4 as Modifier,” Electrochimica Acta 54, no. 17 (2009): 4141–4148.

[44] J. Gao, H. b Yang, X. Huang, et al., “Enabling Direct H2O2 Production in Acidic Media Through Rational Design of Transition Metal Single Atom Catalyst,” Chem 6, no. 3 (2020): 658–674.

[45] Z. Li, X. Lu, C. Guo, et al., “Solvent-Free Selective Hydrogenation of Nitroaromatics to Azoxy Compounds Over Co Single Atoms Decorated on Nb₂O₅ Nanomeshes,” Nature Communications 15, no. 1 (2024): 3195.

[46] C. M. Ramos-Castillo, L. Torres-Pacheco, L. Álvarez-Contreras, N. Arjona, and M. Guerra-Balcázar, “Tuning the d-Band Center of Nickel Bimetallic Compounds for Glycerol Chemisorption: A Density Functional Study,” Molecules [Online] 30, no. 3 (2025): 744.

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