journal article·2026-02-19Open access

Nanomaterials-Enabled Electrochemical Biosensors: From Enhanced Performance to Regulatory Readiness

Virginia Rondinini, Stefano Giordani, Luisa Stella Dolci, Anna Placci, Pierluigi Reschiglian, Barbara Roda, Aldo Roda, Valentina Marassi, Andrea Zattoni

Applied Sciences· Volume 16· Issue 4

Abstract

Electrochemical biosensors represent mature platforms for point-of-need analysis due to their high sensitivity, intrinsic selectivity, low cost, and facile miniaturization. In the last decade, nanomaterials have become integral to advanced biosensor architectures, acting as high-surface-area supports, electron-transfer mediators, and signal-amplifying elements. This review critically examines the most represented nanomaterial classes in mature electrochemical biosensors—carbon nanostructures, gold nanoparticles, and iron-based magnetic nanoparticles—highlighting how morphology, electronic structure, and surface chemistry influence key performance metrics such as limit of detection, linear range, and assay time. Despite a strong technology push and numerous proof-of-concept demonstrations, the translation of nanomaterial-enabled electrochemical biosensors into commercial devices remains limited. This gap arises from the intrinsic physicochemical complexity of nanomaterials, which hampers standardization, reproducibility, and long-term safety assessment. Accordingly, this review integrates performance analysis with a systematic overview of the European regulatory framework, including the Medical Device Regulation (MDR) (EU) 2017/745, the In Vitro Diagnostic Regulation (IVR) (EU) 2017/746, EFSA guidance for food and water applications, and relevant ISO standards, outlining key translational bottlenecks and design principles for deployable biosensing technologies.
Source: crossref · Quality: baseline

Research context

OpenAlex topics: Electrochemical sensors and biosensors · Advanced biosensing and bioanalysis techniques · Biosensors and Analytical Detection

SciVX discovery tags are terminology-based. OpenAlex topics are source-provided classifications.

Affiliations

Department of Chemistry “Giacomo Ciamician”, University of Bologna, 40129 Bologna, Italy

byFlow srl, 40129 Bologna, Italy

INBB—Biostructures and Biosystems National Institute, 00165 Rome, Italy

Department of Industrial Chemistry “Toso Montanari”, University of Bologna, 40129 Bologna, Italy

Funding

European Union—NextGeneration EU

References (83)

Show source-provided references
1. Electrochemical Biosensors10.1039/b714449k ↗
2. Electrochemical Biosensors and Nanobiosensors10.1042/EBC20150008 ↗
3. Electrochemical Biosensors—Principles and Applications10.32725/jab.2008.008 ↗
4. Wang, K., Lin, X., Zhang, M., Li, Y., Luo, C., and Wu, J. (2022). Review of Electrochemical Biosensors for Food Safety Detection. Biosensors, 12.10.3390/bios12110959 ↗
5. Device Integration of Electrochemical Biosensors10.1038/s44222-023-00032-w ↗
6. Electrochemical Biosensors: Electrode Development, Materials, Design, and Fabrication10.1002/cben.201600009 ↗
7. Recent Advances in Electrochemical Biosensors—A Brief Review10.1016/j.hybadv.2023.100023 ↗
8. A Review of Nanomaterials for Biosensing Applications10.1039/D3TB02648E ↗
9. Next-Generation Nanomaterials-Based Biosensors: Real-Time Biosensing Devices for Detecting Emerging Environmental Pollutants
10. Thermochemiluminescent Semiconducting Polymer Dots as Sensitive Nanoprobes for Reagentless Immunoassay10.1039/C8NR03092H ↗
11. Organically Modified Silica Nanoparticles Doped with New Acridine-1,2-Dioxetane Analogues as Thermochemiluminescence Reagentless Labels for Ultrasensitive Immunoassays10.1007/s00216-014-8406-3 ↗
12. Shining Light on Biosensors: Chemiluminescence and Bioluminescence in Enabling Technologies10.1016/j.trac.2024.117975 ↗
13. Electrochemical Biosensors: Perspective on Functional Nanomaterials for on-Site Analysis10.1186/s40824-019-0181-y ↗
14. Shellaiah, M. (2025). A Review on Biomedical, Biomolecular, and Environmental Monitoring Applications of Cysteamine Functionalized Nanomaterials. Micromachines, 16.10.3390/mi16101144 ↗
15. Electroanalytical Overview: Screen-Printed Electrochemical Sensing Platforms10.1002/celc.202400370 ↗
16. Pour, S.R.S., Calabria, D., Emamiamin, A., Lazzarini, E., Pace, A., Guardigli, M., Zangheri, M., Mirasoli, M., Pour, S.R.S., and Calabria, D. (2023). Electrochemical vs. Optical Biosensors for Point-of-Care Applications: A Critical Review. Chemosensors, 11.10.20944/preprints202307.1536.v1 ↗
17. Electrochemical Biosensors for Point-of-Care Testing10.1007/s42242-024-00301-6 ↗
18. Analytical Evaluation of Sensor Measurements10.1007/s00216-017-0624-z ↗
19. Prospects of Nanomaterials in Biosensors10.1080/00032710701792620 ↗
20. Holzinger, M., Le Goff, A., and Cosnier, S. (2014). Nanomaterials for Biosensing Applications: A Review. Front. Chem., 2.10.3389/fchem.2014.00063 ↗
21. Iron and Iron-Oxide Magnetic Nanoparticles as Signal-Amplification Elements in Electrochemical Biosensing10.1016/j.trac.2015.03.016 ↗
22. Carbon-Based Electrochemical Biosensors as Diagnostic Platforms for Connected Decentralized Healthcare10.1039/D2SD00226D ↗
23. Innovations in Graphene-Based Electrochemical Biosensors in Healthcare Applications10.1007/s00604-025-07141-w ↗
24. Şak, B., Sousa, H.B.A., Prior, J.A.V., Şak, B., Sousa, H.B.A., and Prior, J.A.V. (2025). Carbon Nanomaterial-Based Electrochemical Biosensors for Alzheimer’s Disease Biomarkers: Progress, Challenges, and Future Perspectives. Biosensors, 15.10.3390/bios15100684 ↗
25. Enhanced Direct Electron Transfer of a Multihemic Nitrite Reductase on Single-Walled Carbon Nanotube Modified Electrodes10.1002/elan.201000363 ↗
26. An Efficient Non-Mediated Amperometric Biosensor for Nitrite Determination10.1016/j.bios.2010.01.031 ↗
27. “Plugging into Enzymes”: Nanowiring of Redox Enzymes by a Gold Nanoparticle10.1126/science.1080664 ↗
28. Long-Range Electrical Contacting of Redox Enzymes by SWCNT Connectors10.1002/anie.200353275 ↗
29. Enzyme-Coated Carbon Nanotubes as Single-Molecule Biosensors10.1021/nl034139u ↗
30. Carbon Nanotubes and Their Composites for Flexible Electrochemical Biosensors
31. Electron Transfer Kinetics on Mono- and Multilayer Graphene10.1021/nn504298r ↗
32. Carbon Nanomaterials in Biosensors: Should You Use Nanotubes or Graphene?10.1002/anie.200903463 ↗
33. Production and Processing of Graphene and 2d Crystals10.1016/S1369-7021(13)70014-2 ↗
34. Surface Plasmon Resonance Based Biosensor Technique: A Review10.1002/jbio.201200015 ↗
35. Carbon Nanotube DNA Sensor and Sensing Mechanism10.1021/nl060613v ↗
36. Complementary Detection of Prostate-Specific Antigen Using In2O3 Nanowires and Carbon Nanotubes10.1021/ja053761g ↗
37. Carbon Nanotube Transistors for Biosensing Applications10.1007/s00216-005-3400-4 ↗
38. Graphene Based Electrochemical Sensors and Biosensors: A Review10.1002/elan.200900571 ↗
39. Recent Advances in Graphene-Based Biosensors10.1016/j.bios.2011.05.039 ↗
40. Gold Nanoparticle-Based Biosensors10.1007/BF03214964 ↗
41. Direct Electrochemistry of Horseradish Peroxidase Based on Biocompatible Carboxymethyl Chitosan–Gold Nanoparticle Nanocomposite10.1016/j.bios.2006.02.010 ↗
42. A Comparison of Different Strategies for the Construction of Amperometric Enzyme Biosensors Using Gold Nanoparticle-Modified Electrodes10.1016/j.ab.2004.07.038 ↗
43. Electrical Contacting of Redox Proteins by Nanotechnological Means10.1016/j.copbio.2006.10.008 ↗
44. Gold Nanoparticle-Based Electrochemical Biosensors10.1016/j.electacta.2008.03.005 ↗
45. Multiplexed Discrimination of SARS-CoV-2 Variants via Plasmonic-Enhanced Fluorescence in a Portable and Automated Device10.1038/s41551-023-01092-4 ↗
46. 1T′-Transition Metal Dichalcogenide Monolayers Stabilized on 4H-Au Nanowires for Ultrasensitive SERS Detection10.1038/s41563-024-01860-w ↗
47. Electrochemical Aptasensor for Escherichia Coli O157:H7 Bacteria Detection Using a Nanocomposite of Reduced Graphene Oxide, Gold Nanoparticles and Polyvinyl Alcohol10.1039/D1AY00563D ↗
48. Electrochemical Immunosensors Using Electrodeposited Gold Nanostructures for Detecting the S Proteins from SARS-CoV and SARS-CoV-210.1007/s00216-022-03956-1 ↗
49. Electrochemical Immunosensor Based on Polythionine/Gold Nanoparticles for the Determination of Aflatoxin B110.3390/s8128262 ↗
50. Amouzadeh Tabrizi, M., and Acedo, P. (2022). An Electrochemical Immunosensor for the Determination of Procalcitonin Using the Gold-Graphene Interdigitated Electrode. Biosensors, 12.10.3390/bios12100771 ↗
51. Hemben, A., Ashley, J., and Tothill, I.E. (2017). Development of an Immunosensor for PfHRP 2 as a Biomarker for Malaria Detection. Biosensors, 7.10.3390/bios7030028 ↗
52. Aptamer-Based Impedimetric Sensor for Bacterial Typing10.1021/ac302217u ↗
53. Gold Nanoparticles-Amplified Laccase-Based Electrochemical Biosensor Using Graphitized Carbon@boron Carbide as Electron Transfer Promoter10.1016/j.microc.2024.111976 ↗
54. Electrochemical Immunosensor Based on Screen-Printed Electrodes Modified with Gold Nanoparticles for Highly Sensitive Detection of TGF-α10.1016/j.talo.2025.100590 ↗
55. Biosensors and Bio-Bar Code Assays Based on Biofunctionalized Magnetic Microbeads10.3390/s7040589 ↗
56. Micro- and Nano- Magnetic Particles for Applications in Biosensing10.1002/elan.200603785 ↗
57. Magnetic Particle-Based Hybrid Platforms for Bioanalytical Sensors10.3390/s90402976 ↗
58. A Practical Glucose Biosensor Based on Fe3O4 Nanoparticles and Chitosan/Nafion Composite Film10.1016/j.bios.2009.09.002 ↗
59. Bienzyme Functionalized Three-Layer Composite Magnetic Nanoparticles for Electrochemical Immunosensors10.1016/j.biomaterials.2009.01.002 ↗
60. Porous Magnetic Nanoparticles-Based Electrochemical Biosensor for Determination of Mercury in the Aquatic Environment10.1002/ppsc.202000074 ↗
61. Label-Free Magnetic Nanoparticles-Based Electrochemical Immunosensor for Atrazine Detection10.1007/s00216-021-03838-y ↗
62. Boubezari, I., Bessueille, F., Bonhomme, A., Raimondi, G., Zazoua, A., Errachid, A., Jaffrezic-Renault, N., Boubezari, I., Bessueille, F., and Bonhomme, A. (2020). Laccase-Based Biosensor Encapsulated in a Galactomannan-Chitosan Composite for the Evaluation of Phenolic Compounds. Biosensors, 10.10.3390/bios10060070 ↗
63. Hanoglu, S.B., Man, E., Harmanci, D., Ruzgar, S.T., Sanli, S., Keles, N.A., Ayden, A., Tuna, B.G., Duzgun, O., and Ozkan, O.F. (2022). Magnetic Nanoparticle-Based Electrochemical Sensing Platform Using Ferrocene-Labelled Peptide Nucleic Acid for the Early Diagnosis of Colorectal Cancer. Biosensors, 12.10.3390/bios12090736 ↗
64. Highly Reusable Electrochemical Immunosensor for Ultrasensitive Protein Detection10.1002/adsr.202400004 ↗
65. Designs and Materials of Electrodes for Electrochemical Sensors10.1002/celc.202500230 ↗
66. (2012). Nanotechnologies—Guidance on Physico-Chemical Characterization of Engineered Nanoscale Materials for Toxicologic Assessment (Standard No. ISO/TR 13014:2012(En)). Available online: https://www.iso.org/obp/ui/en/#iso:std:iso:tr:13014:ed-1:v1:en.
67. (2025). Particle Size Analysis—Dynamic Light Scattering (DLS) (Standard No. ISO 22412:2025(En)). Available online: https://www.iso.org/obp/ui/en/#iso:std:iso:22412:ed-3:v1:en.
68. (2020). Nanotechnologies—Measurements of Particle Size and Shape Distributions by Transmission Electron Microscopy (Standard No. ISO 21363:2020(En)). Available online: https://www.iso.org/obp/ui/en/#iso:std:iso:21363:ed-1:v1:en.
69. (2020). Nanotechnologies—Nanoparticles in Powder Form—Characteristics and Measurements (Standard No. ISO 17200:2020(En)). Available online: https://www.iso.org/obp/ui/en/#iso:std:iso:17200:ed-1:v1:en.
70. (2016). General Requirements for the Competence of Reference Material Producers (Standard No. ISO 17034:2016(En)). Available online: https://www.iso.org/obp/ui/en/#iso:std:iso:17034:ed-1:v1:en.
71. (2014). Nanotechnologies—Compilation and Description of Toxicological Screening Methods for Manufactured Nanomaterials (Standard No. ISO/TR 16197:2014(En)). Available online: https://www.iso.org/obp/ui/en/#iso:std:iso:tr:16197:ed-1:v1:en.
72. (2018). Biological Evaluation of Medical Devices—Part 1: Evaluation and Testing Within a Risk Management Process (Standard No. ISO 10993-1:2018(En)). Available online: https://www.iso.org/obp/ui/en/#iso:std:iso:10993:-1:ed-5:v1:en.
73. (2009). Biological Evaluation of Medical Devices—Part 5: Tests for In Vitro Cytotoxicity (Standard No. ISO 10993-5:2009(En)). Available online: https://www.iso.org/obp/ui/en/#iso:std:iso:10993:-5:ed-3:v1:en.
74. (2021). Biological Evaluation of Medical Devices—Part 10: Tests for Irritation and Skin Sensitization (Standard No. ISO 10993-10:2021(En)). Available online: https://www.iso.org/obp/ui/en/#iso:std:iso:10993:-10:ed-4:v1:en.
75. EFSA Scientific Committee (2018). Guidance on risk assessment of nanomaterials to be applied in the food and feed chain: Human and animal health. EFSA J., 16, 5327.
76. (2021). Implementation of the EFSA Scientific Committee guidance on nanomaterials in EFSA’s scientific assessments. EFSA Support. Publ., 18, 6790E.
77. European Parliament and Council (2017). Regulation
78. (EU) 2017/745 on medical devices (Medical Device Regulation, MDR). Off. J. Eur. Union, L 117, 1-175.
79. European Parliament and Council (2017). Regulation
80. (EU) 2017/746 on in vitro diagnostic medical devices (In Vitro Diagnostic Regulation, IVDR). Off. J. Eur. Union, L 117, 176-332.
81. (2016). Medical Devices—Quality Management Systems—Requirements for Regulatory Purposes (Standard No. ISO 13485:2016(En)). Available online: https://www.iso.org/obp/ui/en/#iso:std:iso:13485:ed-3:v1:en.
82. (2019). Medical Devices—Application of Risk Management to Medical Devices (Standard No. ISO 14971:2019(En)). Available online: https://www.iso.org/obp/ui/en/#iso:std:iso:14971:ed-3:v1:en.
83. (2017). General Requirements for the Competence of Testing and Calibration Laboratories (Standard No. ISO/IEC 17025:2017(En)). Available online: https://www.iso.org/obp/ui/en/#iso:std:iso-iec:17025:ed-3:v1:en.10.1007/978-3-662-49054-9_904-1 ↗