A comparative mini review on nanoparticle-based colorimetric sensors for detection of viral nucleic acids and proteins and future advancement using artificial intelligence (AI) and machine learning (ML)

Zia Ul Quasim Syed; Kavya Gavai; Moaz Zia; Nikhil Motwani

A comparative mini review on nanoparticle-based colorimetric sensors for detection of viral nucleic acids and proteins and future advancement using artificial intelligence (AI) and machine learning (ML)

Abstract

Recent advances in nanomaterial-based biosensing have significantly enhanced the sensitivity, specificity, and accessibility of diagnostic technologies, particularly through the integration of colorimetric sensor arrays and artificial intelligence. Creative sensor designs in combination with machine learning now incorporate molecular amplification strategies like rolling circle amplification, strand displacement, and hybridization chain reactions to achieve detection limits in the attomole to femtomolar range, even in undiluted serum and plasma. Thus, taking the technology from bench side to bed side. In this review we will discuss various applications and integration of machine learning and artificial intelligence for diagnostic applications to henceforth improve healthcare.

Keywords

Nanoparticles , Diagnostics , Colorimetric sensors , Point-of-care , Artificial intelligence

References

Ebralidze, I. I., Laschuk, N. O., Poisson, J., & Zenkina, O. V. (2019). Chapter 1—Colorimetric Sensors and Sensor Arrays. In O. V. Zenkina (Ed.), Nanomaterials Design for Sensing Applications (pp. 1–39). Elsevier.
Naveed, A., Syed, Z., Athar, M., Huda, S., Ali, M., Ahmed, M., & Reddy, B. (2014). Materials for Drug & Gene Delivery. In Nanobiotechnology (pp. 32–67).
Wang, Z., Syed, Z., Al Mubarak, Z. H., Lehoczky, L., Rodenbaugh, C., Bunce, R. A., & Krishnan, S. (2024). Integrating colorimetry with surface sensitive transducers: Advancing molecular diagnostics in biofluids. Sensors and Actuators B: Chemical, 419, 136361.
Moitra, P., Alafeef, M., Dighe, K., Frieman, M. B., & Pan, D. (2020). Selective Naked-Eye Detection of SARS-CoV-2 Mediated by N Gene Targeted Antisense Oligonucleotide Capped Plasmonic Nanoparticles. ACS Nano, 14(6), 7617–7627.
Syed, Z. ul Q., Samaraweera, S., Wang, Z., & Krishnan, S. (2024). Colorimetric nano-biosensor for low-resource settings: Insulin as a model biomarker. Sensors & Diagnostics, 3(10), 1659–1671.
Dehghani, Z., Hosseini, M., Mohammadnejad, J., & Ganjali, M. R. (2019). New Colorimetric DNA Sensor for Detection of Campylobacter jejuni in Milk Sample Based on Peroxidase-Like Activity of Gold/Platinium Nanocluster. ChemistrySelect, 4(40), 11687–11692.
Ren, Y., Cao, L., Jiao, R., Zhang, X., Zhao, H. yuan, Liang, Z., Li, G., Ling, N., & Ye, Y. (2024). “Five birds one stone” tri-modal monitoring driven lab-on-magnetic aptasensor for accurate pathogen detection and enhanced germicidal application. Biosensors and Bioelectronics, 248, 115991.
Park, K. S., Kim, M. I., Cho, D.-Y., & Park, H. G. (2011). Label-Free Colorimetric Detection of Nucleic Acids Based on Target-Induced Shielding Against the Peroxidase-Mimicking Activity of Magnetic Nanoparticles. Small, 7(11), 1521–1525.
Deng, H., Shen, W., & Gao, Z. (2015). Colorimetric detection of single nucleotide polymorphisms in the presence of 103-fold excess of a wild-type gene. Biosensors & Bioelectronics, 68, 310–315.
Xu, M., Xing, S., Zhao, Y., & Zhao, C. (2021). Peptide nucleic acid-assisted colorimetric detection of single-nucleotide polymorphisms based on the intrinsic peroxidase-like activity of hemin-carbon nanotube nanocomposites. Talanta, 232, 122420.

Ma, X., Chen, Z., Kannan, P., Lin, Z., Qiu, B., & Guo, L. (2016). Gold Nanorods as Colorful Chromogenic Substrates for Semiquantitative Detection of Nucleic Acids, Proteins, and Small Molecules with the Naked Eye. Analytical Chemistry, 88(6), 3227–3234.
Chen, J., Jackson, A. A., Rotello, V. M., & Nugen, S. R. (2016). Colorimetric Detection of Escherichia coli Based on the Enzyme-Induced Metallization of Gold Nanorods. Small (Weinheim an Der Bergstrasse, Germany), 12(18), 2469–2475.
Szychowski, B., Leng, H., Pelton, M., & Daniel, M.-C. (2018). Controlled etching and tapering of Au nanorods using cysteamine. Nanoscale, 10(35), 16830–16838.
Zhong, J., Rösch, E. L., Viereck, T., Schilling, M., & Ludwig, F. (2021). Toward Rapid and Sensitive Detection of SARS-CoV-2 with Functionalized Magnetic Nanoparticles. ACS Sensors, 6(3), 976–984.
Li, J., Liang, P., Zhao, T., Guo, G., Zhu, J., Wen, C., & Zeng, J. (2023). Colorimetric and Raman dual-mode lateral flow immunoassay detection of SARS-CoV-2 N protein antibody based on Ag nanoparticles with ultrathin Au shell assembled onto Fe3O4 nanoparticles. Analytical and Bioanalytical Chemistry, 415(4), 545–554.
Chang, D., Li, J., Liu, R., Liu, M., Tram, K., Schmitt, N., & Li, Y. (2023). A Colorimetric Biosensing Platform with Aptamers, Rolling Circle Amplification and Urease-Mediated Litmus Test. Angewandte Chemie International Edition, 62(51), e202315185.
Tian, B., Han, Y., Wetterskog, E., Donolato, M., Hansen, M. F., Svedlindh, P., & Strömberg, M. (2018). MicroRNA Detection through DNAzyme-Mediated Disintegration of Magnetic Nanoparticle Assemblies. ACS Sensors, 3(9), 1884–1891.
Liu, L., Xu, Z., Molina Vargas, A. M., Dollery, S. J., Schrlau, M. G., Cormier, D., O’Connell, M. R., Tobin, G. J., & Du, K. (2023). Aerosol Jet Printing-Enabled Dual-Function Electrochemical and Colorimetric Biosensor for SARS-CoV-2 Detection. Analytical Chemistry, 95(32), 11997–12005.
Qin, C., Bian, X., Lv, W., & Li, B. (2024). Label-free chemiluminescent CRISPR/Cas12a biosensing strategy for the detection of nucleic acids and non-nucleic acids utilizing DNAzyme Supernova. Sensors and Actuators B: Chemical, 402, 135143.
Lee, H., Joo, S.-W., Lee, S. Y., Lee, C.-H., Yoon, K.-A., & Lee, K. (2010). Colorimetric genotyping of single nucleotide polymorphism based on selective aggregation of unmodified gold nanoparticles. Biosensors and Bioelectronics, 26(2), 730–735.
Liu, M., Zhao, H., Chen, S., Yu, H., & Quan, X. (2012). Interface Engineering Catalytic Graphene for Smart Colorimetric Biosensing. ACS Nano, 6(4), 3142–3151.
Saha, S., Chakraborty, K., & Krishnan, Y. (2012). Tunable, colorimetric DNA-based pH sensors mediated by A-motif formation. Chemical Communications, 48(19), 2513–2515.
Akiyama, Y., Shikagawa, H., Kanayama, N., Takarada, T., & Maeda, M. (2014). DNA Dangling-End-Induced Colloidal Stabilization of Gold Nanoparticles for Colorimetric Single-Nucleotide Polymorphism Genotyping. Chemistry – A European Journal, 20(52), 17420–17425.
Wang, G., Akiyama, Y., Takarada, T., & Maeda, M. (2016). Rapid Non-Crosslinking Aggregation of DNA-Functionalized Gold Nanorods and Nanotriangles for Colorimetric Single-Nucleotide Discrimination. Chemistry – A European Journal, 22(1), 258–263.
Hizir, M. S., Top, M., Balcioglu, M., Rana, M., Robertson, N. M., Shen, F., Sheng, J., & Yigit, M. V. (2016). Multiplexed Activity of perAuxidase: DNA-Capped AuNPs Act as Adjustable Peroxidase. Analytical Chemistry, 88(1), 600–605.
Yu, T., Dai, P.-P., Xu, J.-J., & Chen, H.-Y. (2016). Highly Sensitive Colorimetric Cancer Cell Detection Based on Dual Signal Amplification. ACS Applied Materials & Interfaces, 8(7), 4434–4441.
Teengam, P., Siangproh, W., Tuantranont, A., Vilaivan, T., Chailapakul, O., & Henry, C. S. (2017). Multiplex Paper-Based Colorimetric DNA Sensor Using Pyrrolidinyl Peptide Nucleic Acid-Induced AgNPs Aggregation for Detecting MERS-CoV, MTB, and HPV Oligonucleotides. Analytical Chemistry, 89(10), 5428–5435.
Wolfe, M. G., Ali, M. M., & Brennan, J. D. (2019). Enzymatic Litmus Test for Selective Colorimetric Detection of C–C Single Nucleotide Polymorphisms. Analytical Chemistry, 91(7), 4735–4740.
Xu, L., Chopdat, R., Li, D., & Al-Jamal, K. T. (2020). Development of a simple, sensitive and selective colorimetric aptasensor for the detection of cancer-derived exosomes. Biosensors & Bioelectronics, 169, 112576.
Gorshkov, K., Susumu, K., Chen, J., Xu, M., Pradhan, M., Zhu, W., Hu, X., Breger, J. C., Wolak, M., & Oh, E. (2020). Quantum Dot-Conjugated SARS-CoV-2 Spike Pseudo-Virions Enable Tracking of Angiotensin Converting Enzyme 2 Binding and Endocytosis. ACS Nano, 14(9), 12234–12247.
Kasiri, M., & Rahaie, M. (2021). A visible and colorimetric nanobiosensor based on DNA-CuO nanoparticle for detection of single nucleotide polymorphism involved in sickle cell anemia disease. Materials Today Communications, 27, 102423.
Karakuş, E., Erdemir, E., Demirbilek, N., & Liv, L. (2021). Colorimetric and electrochemical detection of SARS-CoV-2 spike antigen with a gold nanoparticle-based biosensor. Analytica Chimica Acta, 1182, 338939.
Büyüksünetçi, Y. T., Çitil, B. E., Tapan, U., & Anık, Ü. (2021). Development and application of a SARS-CoV-2 colorimetric biosensor based on the peroxidase-mimic activity of γ-Fe2O3 nanoparticles. Mikrochimica Acta, 188(10), 335.
Rodríguez Díaz, C., Lafuente-Gómez, N., Coutinho, C., Pardo, D., Alarcón-Iniesta, H., López-Valls, M., Coloma, R., Milán-Rois, P., Domenech, M., Abreu, M., Cantón, R., Galán, J. C., Bocanegra, R., Campos, L. A., Miranda, R., Castellanos, M., & Somoza, Á. (2022). Development of colorimetric sensors based on gold nanoparticles for SARS-CoV-2 RdRp, E and S genes detection. Talanta, 243, 123393.
Zhang, T., Deng, R., Wang, Y., Wu, C., Zhang, K., Wang, C., Gong, N., Ledesma-Amaro, R., Teng, X., Yang, C., Xue, T., Zhang, Y., Hu, Y., He, Q., Li, W., & Li, J. (2022). A paper-based assay for the colorimetric detection of SARS-CoV-2 variants at single-nucleotide resolution. Nature Biomedical Engineering, 6(8), 957–967.
Li, J., Khan, S., Gu, J., Filipe, C. D. M., Didar, T. F., & Li, Y. (2023). A Simple Colorimetric Au-on-Au Tip Sensor with a New Functional Nucleic Acid Probe for Food-borne Pathogen Salmonella typhimurium. Angewandte Chemie International Edition, 62(20), e202300828.
Aloraij, Y. M., Suaifan, G. A. R. Y., Shibl, A., Al-Kattan, K., & Zourob, M. M. (2023). Development of Rapid Aptamer-Based Screening Assay for the Detection of Covid-19 Variants. ACS Omega, 8(36), 32877–32883.
Chang, D., Li, J., Liu, R., Liu, M., Tram, K., Schmitt, N., & Li, Y. (2023). A Colorimetric Biosensing Platform with Aptamers, Rolling Circle Amplification and Urease-Mediated Litmus Test. Angewandte Chemie International Edition, 62(51), e202315185.
El Aamri, M., Mohammadi, H., & Amine, A. (2023). A highly sensitive colorimetric DNA sensor for MicroRNA-155 detection: Leveraging the peroxidase-like activity of copper nanoparticles in a double amplification strategy. Mikrochimica Acta, 191(1), 32.
Fan, P., Li, Q., Zhang, Z., Jiang, P., Zhang, Z., Wu, Q., & Li, L. (2024). A G-quadruplex-assisted target-responsive dual-mode aptasensor based on copper nanoclusters synthesized in situ in a DNA hydrogel for ultrasensitive detection of ochratoxin A. Talanta, 270, 125550.
Duan, N., Chang, Y., Su, T., Zhang, X., Lu, M., Wang, Z., & Wu, S. (2024). Generation of a specific aptamer for accurate detection of sarafloxacin based on fluorescent/colorimetric/SERS triple-readout sensor. Biosensors and Bioelectronics, 249, 116022.
Unabia, R. B., Reazo, R. L. D., Rivera, R. B. P., Lapening, M. A., Omping, J. L., Lumod, R. M., Ruda, A. G., Sayson, N. L. B., Dumancas, G., Malaluan, R. M., Lubguban, A. A., Petalcorin, G. C. J., Capangpangan, R. Y., Latayada, F. S., & Alguno, A. C. (2024). Dopamine-Functionalized Gold Nanoparticles for Colorimetric Detection of Histamine. ACS Omega, 9(15), 17238–17246.
Kim, B.-H., Yoon, I. S., & Lee, J.-S. (2013). Masking Nanoparticle Surfaces for Sensitive and Selective Colorimetric Detection of Proteins. Analytical Chemistry, 85(21), 10542–10548.
Büyüksünetçi, Y. T., Çitil, B. E., Tapan, U., & Anık, Ü. (2021a). Development and application of a SARS-CoV-2 colorimetric biosensor based on the peroxidase-mimic activity of γ-Fe2O3 nanoparticles. Mikrochimica Acta, 188(10), 335.
Feng, Y., Qu, X., Peng, Y., Xu, X., Zhang, J., Wang, Y., Zhu, S., Li, M., Li, C., & Feng, N. (2023). Iodide-Enhanced Perovskite Nanozyme-Based Colorimetric Platform for Detection of Urinary Nuclear Matrix Protein 22. ACS Applied Materials & Interfaces, 15(23), 27742–27749.
Liu, X., Wang, Y., Chen, P., McCadden, A., Palaniappan, A., Zhang, J., & Liedberg, B. (2016). Peptide Functionalized Gold Nanoparticles with Optimized Particle Size and Concentration for Colorimetric Assay Development: Detection of Cardiac Troponin I. ACS Sensors, 1(12), 1416–1422.
Mei, W., Zhou, Y., Xia, L., Liu, X., Huang, W., Wang, H., Zou, L., Wang, Q., Yang, X., & Wang, K. (2023). DNA Tetrahedron-Based Valency Controlled Signal Probes for Tunable Protein Detection. ACS Sensors, 8(1), 381–387.
Yin, W., Li, L., Yang, Y., Yang, Y., Liang, R., Ma, L., Dai, J., Mao, G., & Ma, Y. (2024). Ultra-Sensitive Detection of the SARS-CoV-2 Nucleocapsid Protein via a Clustered Regularly Interspaced Short Palindromic Repeat/Cas12a-Mediated Immunoassay. ACS Sensors, 9(6), 3150–3157.
Chen, J., Ren, B., Wang, Z., Wang, Q., Bi, J., & Sun, X. (2023). Multiple Isothermal Amplification Coupled with CRISPR–Cas14a for the Naked-eye and Colorimetric Detection of Aflatoxin B1. ACS Applied Materials & Interfaces, 15(48), 55423–55432.
Wu, F., Mao, M., Cai, L., Lin, Q., Guan, X., Shi, X., & Ma, L. (2022). Platinum-Decorated Gold Nanoparticle-Based Microfluidic Chip Immunoassay for Ultrasensitive Colorimetric Detection of SARS-CoV-2 Nucleocapsid Protein. ACS Biomaterials Science & Engineering, 8(9), 3924–3932.
Wu, S., Tan, H., Wang, C., Wang, J., & Sheng, S. (2019). A Colorimetric Immunoassay Based on Coordination Polymer Composite for the Detection of Carcinoembryonic Antigen. ACS Applied Materials & Interfaces, 11(46), 43031–43038.
Dadmehr, M., Mortezaei, M., & Korouzhdehi, B. (2023). Dual mode fluorometric and colorimetric detection of matrix metalloproteinase MMP-9 as a cancer biomarker based on AuNPs@gelatin/AuNCs nanocomposite. Biosensors and Bioelectronics, 220, 114889.
Yu, X., Pan, B., Zhao, C., Shorty, D., Solano, L. N., Sun, G., Liu, R., & Lam, K. S. (2023). Discovery of Peptidic Ligands against the SARS-CoV-2 Spike Protein and Their Use in the Development of a Highly Sensitive Personal Use Colorimetric COVID-19 Biosensor. ACS Sensors, 8(6), 2159–2168.
Cai, Z., Sasmal, A., Liu, X., & Asher, S. A. (2017). Responsive Photonic Crystal Carbohydrate Hydrogel Sensor Materials for Selective and Sensitive Lectin Protein Detection. ACS Sensors, 2(10), 1474–1481.
Gao, H., Ta, L., Li, Z., Zhu, B., Lu, H., Ding, T., Deng, X., Li, X., Han, F., & Xu, D. (2022). Simultaneous Detection of Four Mycotoxins in Cereals and Edible Oils by Using a Colorimetric Protein Microarray. ACS Food Science & Technology, 2(6), 993–999.
Son, S. E., Gupta, P. K., Hur, W., Lee, H. B., Han, D. K., & Seong, G. H. (2023). Hollow Ruthenium Nanoparticles with Enhanced Catalytic Activity for Colorimetric Detection of C-Reactive Protein. ACS Applied Nano Materials, 6(13), 11435–11442.
Akhtar, A. S., Soares, R. R. G., Pinto, I. F., & Russom, A. (2023). A portable and low-cost centrifugal microfluidic platform for multiplexed colorimetric detection of protein biomarkers. Analytica Chimica Acta, 1245, 340823.
Guo, G., Zhao, T., Sun, R., Song, M., Liu, H., Wang, S., Li, J., & Zeng, J. (2024). Au-Fe3O4 dumbbell-like nanoparticles based lateral flow immunoassay for colorimetric and photothermal dual-mode detection of SARS-CoV-2 spike protein. Chinese Chemical Letters, 35(6), 109198.
Urusov, A. E., Zherdev, A. V., & Dzantiev, B. B. (2019). Towards Lateral Flow Quantitative Assays: Detection Approaches. Biosensors, 9(3), Article 3.
Liu, Y., Zhan, L., Qin, Z., Sackrison, J., & Bischof, J. C. (2021). Ultrasensitive and Highly Specific Lateral Flow Assays for Point-of-Care Diagnosis. ACS Nano, 15(3), 3593–3611.
Lee, S., Park, J. S., Woo, H., Yoo, Y. K., Lee, D., Chung, S., Yoon, D. S., Lee, K.-B., & Lee, J. H. (2024). Rapid deep learning-assisted predictive diagnostics for point-of-care testing. Nature Communications, 15(1), 1695.
Yang, J., Li, G., Chen, S., Su, X., Xu, D., Zhai, Y., Liu, Y., Hu, G., Guo, C., Yang, H. B., Occhipinti, L. G., & Hu, F. X. (2024). Machine Learning-Assistant Colorimetric Sensor Arrays for Intelligent and Rapid Diagnosis of Urinary Tract Infection. ACS Sensors, 9(4), 1945–1956.
Yang, J., Li, G., Chen, S., Su, X., Xu, D., Zhai, Y., Liu, Y., Hu, G., Guo, C., Yang, H. B., Occhipinti, L. G., & Hu, F. X. (2024). Machine Learning-Assistant Colorimetric Sensor Arrays for Intelligent and Rapid Diagnosis of Urinary Tract Infection. ACS Sensors, 9(4), 1945–1956.
Wei, X., Wang, Y., Zhao, Y., & Chen, Z. (2017). Colorimetric sensor array for protein discrimination based on different DNA chain length-dependent gold nanoparticles aggregation. Biosensors and Bioelectronics, 97, 332–337.
Draz, M. S., Vasan, A., Muthupandian, A., Kanakasabapathy, M. K., Thirumalaraju, P., Sreeram, A., Krishnakumar, S., Yogesh, V., Lin, W., Yu, X. G., Chung, R. T., & Shafiee, H. (2020). Virus detection using nanoparticles and deep neural network–enabled smartphone system. Science Advances, 6(51), eabd5354.
Davis, A. M., & Tomitaka, A. (2025). Machine Learning-Based Quantification of Lateral Flow Assay Using Smartphone-Captured Images. Biosensors, 15(1), Article 1.
Xue, M., Gonzalez, D. H., Osikpa, E., Gao, X., & Lillehoj, P. B. (2025). Rapid and automated interpretation of CRISPR-Cas13-based lateral flow assay test results using machine learning. Sensors & Diagnostics, 4(2), 171–181.
Zhang, T., Deng, R., Wang, Y., Wu, C., Zhang, K., Wang, C., Gong, N., Ledesma-Amaro, R., Teng, X., Yang, C., Xue, T., Zhang, Y., Hu, Y., He, Q., Li, W., & Li, J. (2022). A paper-based assay for the colorimetric detection of SARS-CoV-2 variants at single-nucleotide resolution. Nature Biomedical Engineering, 6(8), 957–967.
Lee, S., Kim, S., Yoon, D. S., Park, J. S., Woo, H., Lee, D., Cho, S.-Y., Park, C., Yoo, Y. K., Lee, K.-B., & Lee, J. H. (2023). Sample-to-answer platform for the clinical evaluation of COVID-19 using a deep learning-assisted smartphone-based assay. Nature Communications, 14(1), 2361.
Shen, Y., Huang, Y., Zhang, P., Guo, B., Jiang, H., Tan, C., & Jiang, Y. (2020). Fluorescence Sensor Array for Discrimination of Urine Proteins and Differentiation Diagnosis of Urinary System Diseases. ACS Applied Bio Materials, 3(9), 5639–5643.

Details

Primary Language

English

Subjects

Sensor Technology

Journal Section

Review

Authors

Zia Ul Quasim Syed ^*
0000-0003-3211-5526
United States

Kavya Gavai This is me
0009-0001-3611-5905
United States

Moaz Zia This is me
0009-0001-6761-0378
United States

Nikhil Motwani
0009-0008-9628-1156
United States

Publication Date

June 25, 2025

Submission Date

June 1, 2025

Acceptance Date

June 21, 2025

Published in Issue

Year 2025 Volume: 2 Number: 1

IZ

https://izlik.org/JA77ZZ73FB

APA

Syed, Z. U. Q., Gavai, K., Zia, M., & Motwani, N. (2025). A comparative mini review on nanoparticle-based colorimetric sensors for detection of viral nucleic acids and proteins and future advancement using artificial intelligence (AI) and machine learning (ML). Turkish Journal of Sensors and Biosensors, 2(1), 18-30. https://izlik.org/JA77ZZ73FB

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