COPPER-ENHANCED GOLD NANOPARTICLES AND RECOMBINANT BIOPRODUCTS: PROMISE FOR RAPID, HIGHLY SENSITIVE TESTING
Main Article Content
Abstract
Diseases such as tuberculosis and Alzheimer's require early detection with high sensitivity for timely intervention, however, current techniques such as ELISA, PCR are limited in cost and sensitivity. Recent advances in nanotechnology have shown that copper-shelled gold nanoparticles combined with recombinant biologicals (proteins or aptamers) can amplify the color signal, opening up prospects for ultra-sensitive early diagnosis. This review analyzes the technical mechanism of antigen testing by forming copper nanoshells on gold particles, in which Cu²⁺ ions are reduced by sodium ascorbate on the surface of AuNPs with the role of stabilizing polyethylenimine, creating a polygonal Au-Cu structure to enhance the plasmon signal. Two variants were investigated: the recombinant antibody system GBP-CFP10G2/GBP-50B14 detecting tuberculosis antigens CFP-10, Ag85B, and the aptamer system recognizing p-tau231 or AβO42 in Alzheimer's. These systems achieve detection limits as low as picograms/mL and can be observed with the naked eye. The Au@Cu method shows outstanding advantages in terms of sensitivity, low cost and integration with paper or mobile platforms, but challenges still exist in the stability of the copper layer, crossreactivity and process standardization. Future prospects aim at improving nanomaterials, automating microchannel-based processes and applying artificial intelligence in signal quantification, towards a rapid, accurate and cost-friendly testing platform for early diagnosis in the community.
Keywords
copper coated gold nanoparticle, recombinant protein, aptamer, color enhancer, early diagnosis
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References
2. World Health Organization. Tuberculosis. 2024. https://www.who.int/news-room/factsheets/detail/tuberculosis.
3. Zewei Yang, J.L., Jiawen Shen, Huiru Cao, Yuhan Wang, Sensen Hu, Yulu Du, Yange Wang, Zhongyi Yan, Longxiang Xie, Qiming Li, Salwa E. Gomaa, Shejuan Liu, Xianghui Li and Jicheng Li. Recent progress in tuberculosis diagnosis: insights into blood-based biomarkers and emerging technologies. Frontiers in Cellular and Infection Microbiology. 2025. 15,1567592. DOI: 10.3389/fcimb.2025.1567592
4. K.V.L. Keerthi, N.N.S., O Brunda Sree, Naguru Subbamma, O. Adithya Karthikeya and Abhinaya Varma N. Early Detection of Tuberculosis Using SVM and FCM. Proceedings of the 1st International Conference on Research and Development in Information. Communication, and Computing Technologies. 2025.
5. Bruno Dubois, C.A.F.v.A., Nerida Burnie, Sasha Bozeat and Jeffrey Cummings. Biomarkers in Alzheimer’s disease: role in early and differential diagnosis and recognition of atypical variants. Alzheimer’s Research & Therapy. 2023. 15(1),175. DOI: 10.1186/s13195-023-01314-6.
6. Karim Gasmi, A.A., Najib Ben Aoun, Mohamed O. Altaieb, Alameen E. M. Abdalrahman, Omer Hamid, Sahar Almenwer, Lassaad Ben Ammar, Samia Yahyaoui and Manel Mrabet. Early Tuberculosis Detection via Privacy-Preserving, Adaptive-Weighted Deep Models. Diagnostics. 2026. 16(2), 204. DOI: 10.3390/diagnostics16020204.
7. Phan, L.M.T., et al. Nanomaterial-based Optical and Electrochemical Biosensors for Amyloid beta and Tau: Potential for early diagnosis of Alzheimer’s Disease. Expert Review of Molecular Diagnostics. 2021. 21(2), 175-193. DOI: 10.1080/14737159.2021.1887732.
8. Chuntae Kim, M.S.K., Iruthayapandi Selestin Raja, Yoon Ki Joung, Dong-Wook Han, Advancements in nanobiosensor technologies for in-vitro diagnostics to point of care testing. Heliyon. 2024. 10(22), e40306. DOI: 10.1016/j.heliyon.2024.e40306.
9. Mansi Parihar, N.W.N., Sahana, Rajib Biswas, Budheswar Dehury and Nirmal Mazumder. Point-of-care biosensors for infectious disease diagnosis: recent updates and prospects. Royal Society of Chemistry. 2025. 15(36),29267–29283. DOI: 10.1039/d5ra03897a.
10. Yubeen Lee, I.H., Sang Baek Sim and Jin-Ha Choi. Colorimetric Biosensors: Advancements in Nanomaterials and Cutting-Edge Detection Strategies. Biosensors. 2025. 15(6), 362. DOI: 10.3390/bios15060362
11. Phan, L.-M.-T. and S. Cho. A Multi-Chamber Paper-Based Platform for the Detection of Amyloid β Oligomers 42 via Copper-Enhanced Gold Immunoblotting. Biomolecules. 2021. 11(7),948. DOI: 10.3390/biom11070948
12. Le Minh Tu Phan, L.M.T.P., et al. Gold-copper nanoshell dot-blot immunoassay for naked-eye sensitive detection of tuberculosis specific CFP-10 antigen. Biosens Bioelectron. 2018. 121,111-117. DOI: 10.1016/j.bios.2018.08.068.
13. Phan, L.M.T., et al. Reliable naked-eye detection of Mycobacterium tuberculosis antigen 85B using gold and copper nanoshell-enhanced immunoblotting techniques. Sensors and Actuators B: Chemical. 2020. 317, 128220. DOI:10.1016/j.snb.2020.128220.
14. Surti, P.V., et al. Progress on dot-blot assay as a promising analytical tool: Detection from molecules to cells. TrAC Trends in Analytical Chemistry. 2022. 157, 116736. DOI:10.1016/j.trac.2022.116736.
15. Rudroju Anusha, A.Y., Eragari Nikhitha, Bheemari Harshitha, Algola Vamshi Krishna, Dudekula Baji Baba. A review on core shell nanoparticles: classes, synthesis, characterization of core shell nanoparticles. International Journal of Basic & Clinical Pharmacology. 2025. 14(4), 614-622. DOI:10.18203/2319-2003.ijbcp20251848
16. Hatice Duman, E.A.s., Furkan Eker , Mikhael Bechelany, and Sercan Karav. Gold Nanoparticles: Multifunctional Properties, Synthesis, and Future Prospects. Nanomaterials. 2024. 14(22),1805. DOI: 10.3390/nano14221805.
17. Rui Wu, Q.D., Hairan Zhang, Pengfei Zhang, Xiaoyun Lei, Fagen Zhang. A comprehensive Review: The approach for fabrication of Core/Shell Au nanocomposite and Modification, Properties, applications of Au NPs. Journal of Saudi Chemical Society. 2024. (4),614-622. DOI:10.18203/2319-2003.ijbcp20251848.
18. Duan, H., et al. Avoiding the self-nucleation interference: a pH-regulated gold in situ growth strategy to enable ultrasensitive immunochromatographic diagnostics. Theranostics. 2022. 12(6), 2801. DOI: 10.7150/thno.70092.
19. Ferrari, E. Gold nanoparticle-based plasmonic biosensors. Biosensors. 2023. 13(3), 411. DOI: 10.3390/bios13030411.
20. Sathishkumar, N. and B.J. Toley. Direct comparison of colorimetric signal amplification techniques in lateral flow immunoassays. Analytical Methods. 2024. 16(42), 7200-7209. DOI:10.1039/D4AY01416B.
21. Mir Hadi Jazayeri, H.A., Ali Akbar Pourfatollah, and B.S. Hamidreza Pazoki-Toroudi e, Various methods of gold nanoparticles (GNPs) conjugation to antibodies. Sensing and BioSensing Research. 2016. DOI:10.1016/j.sbsr.2016.04.002.
22. Phan, L.M.T. and S. Cho. Fluorescent aptasensor and colorimetric aptablot for p-tau231 detection: Toward early diagnosis of Alzheimer’s disease. Biomedicines. 2022. 10(1), 93. DOI: 10.3390/biomedicines10010093.
23. Sati, A., et al. From Past to Present: Gold Nanoparticles (AuNPs) in Daily Life-Synthesis Mechanisms, Influencing Factors, Characterization, Toxicity, and Emerging Applications in Biomedicine, Nanoelectronics, and Materials Science. ACS Omega. 2025. 10(31), 3399934087. DOI: 10.1021/acsomega.5c03162.
24. Zhang, Y., I.D. McKelvie, R.W. Cattrall, and S.D. Kolev. Colorimetric detection based on localised surface plasmon resonance of gold nanoparticles: Merits, inherent shortcomings and future prospects. Talanta. 2016. 152, 410-422. DOI: 1016/j.talanta.2016.02.015.
25. Kant, T., K. Shrivas, and N.S. Dahariya. Localized Surface Plasmon Resonance (LSPR) of Nanomaterials for Colorimetric Detection: A Review. Current Indian Science. 2024. 2(1), e2210299X281976. DOI:10.2174/012210299X281976240527072849.
26. Kim, M.W., et al. Fabrication of a paper strip for facile and rapid detection of bovine viral diarrhea virus via signal enhancement by copper polyhedral nanoshells. RSC advances. 2020. 10(50), 29759-29764. DOI: 10.1039/d0ra03677c.
27. Scherrer, S., P. Landolt, U. Friedel, and R. Stephan. Distribution and expression of esat-6 and cfp-10 in non-tuberculous mycobacteria isolated from lymph nodes of slaughtered cattle in Switzerland. Journal of Veterinary Diagnostic Investigation. 2019. 31(2), 217-221. DOI: 10.1177/1040638718824074.
28. Zhang, W., et al. Antigen 85B peptidomic analysis allows species-specific mycobacterial identification. Clinical Proteomics. 2018. 15(1), 1. DOI: 10.1186/s12014-017-9177-6.
29. Jenkins, A.O., et al. Cross reactive immune responses in cattle arising from exposure to Mycobacterium bovis and non-tuberculous mycobacteria. Preventive Veterinary Medicine. 2018. 152, 16-22. DOI: 10.1016/j.prevetmed.2018.02.003.
30. Kumar, G., et al. Serodiagnostic efficacy of Mycobacterium tuberculosis 30/32-kDa mycolyl transferase complex, ESAT-6, and CFP-10 in patients with active tuberculosis. Archivum immunologiae et therapiae experimentalis. 2010. 58(1), 57-65. DOI: 10.1007/s00005-009-0055-4.
31. Sun, J., et al. Diagnostic value of tuberculosis-Specific antigens Ag85B, ESAT-6 and CFP10 in pulmonary tuberculosis. Journal of Clinical Tuberculosis and Other Mycobacterial Diseases. 2024. 37, 100486. DOI: 10.1016/j.jctube.2024.100486
32. Parakh, A., et al. Artificial Intelligence and Machine Learning for Colorimetric Detections: Techniques, Applications, and Future Prospects. Trends in Environmental Analytical Chemistry. 2025. e00280. DOI:10.1016/j.teac.2025.e00280.