Multiplexed Detection of MicroRNA Biomarkers Using SERS-Based Inverse Molecular Sentinel (iMS) Nanoprobes
Open accessAbstract
MicroRNAs (miRNAs) have demonstrated great promise as a novel class of biomarkers for early detection of various cancers, including breast cancer. However, due to technical difficulties in detecting these small molecules, miRNAs have not been adopted into routine clinical practice for early diagnostics. Thus, it is important to develop alternative detection strategies that could offer more advantages over conventional methods. Here, we demonstrate the application of a "turn-on" SERS sensing technology, referred to as "inverse Molecular Sentinel (iMS)" nanoprobes, as a homogeneous assay for multiplexed detection of miRNAs. This SERS nanoprobe involves the use of plasmonic-active nanostars as the sensing platform. The "OFF-to-ON" signal switch is based on a nonenzymatic strand-displacement process and the conformational change of stem-loop (hairpin) oligonucleotide probes upon target binding. This technique was previously used to detect a synthetic DNA sequence of interest. In this study, we modified the design of the nanoprobe to be used for the detection of short (22-nt) miRNA sequences. The demonstration of using iMS nanoprobes to detect miRNAs in real biological samples was performed with total small RNA extracted from breast cancer cell lines. The multiplex capability of the iMS technique was demonstrated using a mixture of the two differently labeled nanoprobes to detect miR-21 and miR-34a miRNA biomarkers for breast cancer. The results of this study demonstrate the feasibility of applying the iMS technique for multiplexed detection of short miRNAs molecules.
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Plasmonic nanobiosensors for detection of microRNA cancer biomarkers in clinical samples
Crawford, B. M., Wang, H., Stolarchuk, C., von Furstenberg, R. J., Strobbia, P., Zhang, D., Qin, X., Owzar, K., Garman, K. S., & Vo‐Dinh, T. (2020) · The Analyst · doi:10.1039/d0an00193g · Cited by 37 · see citing works
Self-citationPlasmonic nanoplatforms: From surface‐enhanced Raman scattering sensing to biomedical applications
Cupil‐Garcia, V., Strobbia, P., Crawford, B. M., Wang, H., Ngo, H., Liu, Y., & Vo‐Dinh, T. (2021) · Journal of Raman Spectroscopy · doi:10.1002/jrs.6056 · Cited by 34 · see citing works
Self-citationNanomaterial-based multiplex optical sensors
Pei, X., Tao, G., Wu, X., Ma, Y., Li, R. S., & Li, N. (2020) · The Analyst · doi:10.1039/d0an00392a · Cited by 33 · see citing works
Atta, S., Watcharawittayakul, T., & Vo‐Dinh, T. (2022) · The Analyst · doi:10.1039/d2an00794k · Cited by 33 · see citing works
Self-citationMohammadniaei, M., Yoon, J., Lee, T., & Choi, J. (2018) · Journal of Biotechnology · doi:10.1016/j.jbiotec.2018.03.014 · Cited by 32 · see citing works
Xu, W. L., Zhao, A., Zuo, F., Khan, R., Hussain, H. M. J., & Chang, J. (2020) · Microchimica Acta · doi:10.1007/s00604-020-04330-7 · Cited by 32 · see citing works
Mohammadniaei, M., Go, A., Chavan, S. G., Koyappayil, A., Kim, S.-E., Yoo, H. J., Min, J., & Lee, M. (2019) · Biosensors and Bioelectronics · doi:10.1016/j.bios.2019.111468 · Cited by 31 · see citing works
Yang, Q., Hao, Y., Chen, Z., Lan, N., He, X., Hu, D., Xu, Z., Liang, L., Cao, D., Guo, J., et al. (2023) · Sensors and Actuators B Chemical · doi:10.1016/j.snb.2023.134248 · Cited by 30 · see citing works
Electrochemical nucleic acid detection based on parallel structural dsDNA/recombinant azurin hybrid
Mohammadniaei, M., Lee, T., Yoon, J., Lee, D., & Choi, J. (2017) · Biosensors and Bioelectronics · doi:10.1016/j.bios.2017.07.005 · Cited by 29 · see citing works
Krishnan, T., Wang, H., & Vo‐Dinh, T. (2021) · Sensors · doi:10.3390/s21238044 · Cited by 28 · see citing works
Self-citationZhang, H., Fu, C., Yu, Y., Zhou, X., Zhou, C. H., Ying, G., Shen, Y., & Zhu, Y. (2018) · Analytical Methods · doi:10.1039/c7ay02727c · Cited by 27 · see citing works
Rapid Nanophotonics Assay for Head and Neck Cancer Diagnosis
Vohra, P., Strobbia, P., Ngo, H. T., Lee, W. T., & Vo‐Dinh, T. (2018) · Scientific Reports · doi:10.1038/s41598-018-29428-0 · Cited by 26 · see citing works
Self-citationMagnetic-capture-based SERS detection of multiple serum microRNA biomarkers for cancer diagnosis
Zhang, H., Fu, C., Wu, S., Shen, Y., Zhou, C., Neng, J., Yu, Y., Jin, Y., & Zhu, Y. (2019) · Analytical Methods · doi:10.1039/c8ay02423e · Cited by 25 · see citing works
Aioub, M., Austin, L. A., & El‐Sayed, M. A. (2018) · Elsevier eBooks · doi:10.1016/b978-0-12-813661-4.00002-x · Cited by 22 · see citing works
Inverse surface‐enhanced spatially offset Raman spectroscopy (SESORS) through a monkey skull
Odion, R., Strobbia, P., Crawford, B. M., & Vo‐Dinh, T. (2018) · Journal of Raman Spectroscopy · doi:10.1002/jrs.5402 · Cited by 22 · see citing works
Self-citationOptical nanoantenna for beamed and surface‐enhanced Raman spectroscopy
Awasthi, V., Goel, R., Agarwal, S., Rai, P., & Dubey, S. K. (2020) · Journal of Raman Spectroscopy · doi:10.1002/jrs.5932 · Cited by 21 · see citing works
Li, J. Q., Neng-Wang, H., Canning, A. J., Gaona, A., Crawford, B. M., Garman, K. S., & Vo‐Dinh, T. (2023) · Applied Spectroscopy · doi:10.1177/00037028231209053 · Cited by 20 · see citing works
Self-citationSpectroscopic Chemical Sensing and Imaging: From Plants to Animals and Humans
Strobbia, P., Odion, R., & Vo‐Dinh, T. (2018) · Chemosensors · doi:10.3390/chemosensors6010011 · Cited by 20 · see citing works
Self-citationMercadal, P. A., Encina, E. R., Villa, J. E. L., & Coronado, E. A. (2021) · The Journal of Physical Chemistry C · doi:10.1021/acs.jpcc.0c09122 · Cited by 19 · see citing works
Wang, H., Crawford, B. M., Norton, S. J., & Vo‐Dinh, T. (2019) · The Journal of Physical Chemistry B · doi:10.1021/acs.jpcb.9b06804 · Cited by 19 · see citing works
Self-citationPlasmonic assay for amplification-free cancer biomarkers detection in clinical tissue samples
Dukes, P. V., Strobbia, P., Ngo, H. T., Odion, R. A., Rocke, D., Lee, W. T., & Vo-Dinh, T. (2020) · Analytica Chimica Acta · doi:10.1016/j.aca.2020.09.003 · Cited by 20 · see citing works
Self-citationVo‐Dinh, T., & Inman, B. A. (2017) · Nanomedicine · doi:10.2217/nnm-2017-0356 · Cited by 18 · see citing works
Self-citationRecent Advances Towards Point-Of-Care Applications of Surface-Enhanced Raman Scattering Sensing
Quarin, S. M., & Strobbia, P. (2021) · Frontiers in Chemistry · doi:10.3389/fchem.2021.714113 · Cited by 17 · see citing works
Quarin, S. M., Macke, A. C., Kissell, L. N., Kelly, M. S., Dayananda, A., Ungvary, J., Stan, G., Dima, R. I., & Strobbia, P. (2023) · ACS Sensors · doi:10.1021/acssensors.3c00175 · Cited by 16 · see citing works
Nanoplasmonics biosensors: At the frontiers of biomedical diagnostics
Canning, A. J., Li, J. Q., Atta, S., Wang, H., & Vo‐Dinh, T. (2024) · TrAC Trends in Analytical Chemistry · doi:10.1016/j.trac.2024.117973 · Cited by 16 · see citing works
Self-citationPaccotti, N., Chiadò, A., Novara, C., Rivolo, P., Montesi, D., Geobaldo, F., & Giorgis, F. (2021) · Biosensors · doi:10.3390/bios11120520 · Cited by 15 · see citing works
Liu, X., Jia, Y., & Zheng, C. (2024) · Frontiers in Oncology · doi:10.3389/fonc.2024.1400498 · Cited by 13 · see citing works
Dimensional Surface‐Enhanced Raman Scattering Nanostructures for MicroRNA Profiling
Li, C., Li, S., Qu, A., Xu, C., Xu, L., & Kuang, H. (2021) · Small Structures · doi:10.1002/sstr.202000150 · Cited by 12 · see citing works
SERS in Plain Sight: A Polarization Modulation Method for Signal Extraction
Strobbia, P., Sadler, T., Odion, R., & Vo‐Dinh, T. (2019) · Analytical Chemistry · doi:10.1021/acs.analchem.8b04360 · Cited by 11 · see citing works
Self-citationDirect SERDS sensing of molecular biomarkers in plants under field conditions
Strobbia, P., Odion, R., Maiwald, M., Sumpf, B., & Vo‐Dinh, T. (2020) · Analytical and Bioanalytical Chemistry · doi:10.1007/s00216-020-02544-5 · Cited by 11 · see citing works
Self-citationLi, J. Q., Cupil‐Garcia, V., Wang, H., Strobbia, P., Lai, B. C. H., Hu, J., Maiwald, M., Sumpf, B., Sun, T., Kemner, K., et al. (2024) · Biosensors and Bioelectronics · doi:10.1016/j.bios.2024.116471 · Cited by 9 · see citing works
Self-citationWu, L., He, C., Zhao, T., Li, T., Xu, H., Wen, J., Xu, X., & Gao, L. (2024) · Journal of Nanobiotechnology · doi:10.1186/s12951-024-02644-9 · Cited by 9 · see citing works
Surface Enhanced Raman Spectroscopy for Medical Diagnostics
Jahn, M., Radu, A. I., Weber, K., Cialla‐May, D., & Popp, J. (2018) · Springer eBooks · doi:10.1007/978-3-662-56333-5_1 · Cited by 8 · see citing works
Cancer signaling by plasmonic quantum probes
Agarwal, A., Venkatakrishnan, K., & Tan, B. (2019) · Applied Materials Today · doi:10.1016/j.apmt.2019.100465 · Cited by 8 · see citing works
Huynh, P. T., Nguyen, G. D., Tran, K. T. L., Ho, T. M., Lam, Q. V., & Ngo, T. V. K. (2021) · Processes · doi:10.3390/pr9010112 · Cited by 8 · see citing works
Crawford, B. M., Wang, H., Fales, A. M., Bowie, M. L., Seewaldt, V. L., & Vo‐Dinh, T. (2017) · Proceedings of SPIE, the International Society for Optical Engineering/Proceedings of SPIE · doi:10.1117/12.2258272 · Cited by 7 · see citing works
Self-citationMa, X., Zhang, J., & Wang, Z. (2021) · Spectrochimica Acta Part A Molecular and Biomolecular Spectroscopy · doi:10.1016/j.saa.2021.120195 · Cited by 7 · see citing works
SERS-Based Biosensors as Potential Next-Generation Point-of-Care Cancer Diagnostic Platforms
Roy, S., & Jaiswal, A. K. (2017) · Springer eBooks · doi:10.1007/978-981-10-4726-8_8 · Cited by 6 · see citing works
Cho, J. E., & Lim, D. (2024) · Journal of Materials Chemistry B · doi:10.1039/d4tb01514b · Cited by 5 · see citing works
Cascade Amplified Plasmonics Molecular Biosensor for Sensitive Detection of Disease Biomarkers
Wang, H., & Vo‐Dinh, T. (2023) · Biosensors · doi:10.3390/bios13080774 · Cited by 5 · see citing works
Self-citationWang, H., Register, J. K., Fales, A. M., Gandra, N., Strobbia, P., Cho, E. H., Boico, A., Palmer, G. M., Klitzman, B. M., & Vo‐Dinh, T. (2019) · Plasmonics in Biology and Medicine · doi:10.1117/12.2514634 · Cited by 5 · see citing works
Self-citationSethi, S., Wijesinghe, K. M., Islam, M. M., Harrell, J. C., & Dhakal, S. (2025) · Analytical Chemistry · doi:10.1021/acs.analchem.5c01039 · Cited by 4 · see citing works
Easy-to-make-and-use gold nanotrench arrays for surface-enhanced Raman scattering
Wi, J., Chung, C., Na, H., & Oh, T.-S. (2021) · Optical Materials Express · doi:10.1364/ome.439069 · Cited by 4 · see citing works
Multiplexed detection of single-point mutations in unprocessed human serum with SERS-integrated PCR
Barea, J. S., Lee, A., & Kang, D. (2023) · Sensors and Actuators B Chemical · doi:10.1016/j.snb.2023.134954 · Cited by 4 · see citing works
Barea, J. S., & Kang, D. (2021) · Bulletin of the Korean Chemical Society · doi:10.1002/bkcs.12298 · Cited by 4 · see citing works
Pisarev, E., Kapitanova, O. O., Vesolova, I. A., & Zvereva, M. I. (2021) · Moscow University Chemistry Bulletin · doi:10.3103/s0027131421060079 · Cited by 3 · see citing works
Wang, Y., Chen, B., Jiang, F., & Wang, Z. (2023) · Frontiers in Bioengineering and Biotechnology · doi:10.3389/fbioe.2023.1146111 · Cited by 3 · see citing works
Plasmonic Nanobiosensing: from in situ plant monitoring to cancer diagnostics at the point of care
Crawford, B. M., Wang, H., Strobbia, P., Zentella, R., Pei, Z., Sun, T., & Vo‐Dinh, T. (2020) · Journal of Physics Photonics · doi:10.1088/2515-7647/ab9714 · Cited by 3 · see citing works
Self-citationKissell, L. N., Sheokand, M., & Strobbia, P. (2023) · Journal of Raman Spectroscopy · doi:10.1002/jrs.6539 · Cited by 2 · see citing works
Surface-enhanced patially offset Raman spectroscopy (SESORS) for biomedical applications
Odion, R., Vo‐Dinh, T., & Strobbia, P. (2018) · Advanced Biomedical and Clinical Diagnostic and Surgical Guidance Systems · doi:10.1117/12.2300088 · Cited by 2 · see citing works
Self-citationMolecular SERS Nanoprobes for Medical Diagnostics
Wang, H., Crawford, B. M., & Vo‐Dinh, T. (2017) · CRC Press eBooks · doi:10.1201/9781315374581-15 · Cited by 2 · see citing works
Self-citationInman, B. A., Vo‐Dinh, T., Maccarini, P. F., Palmer, G. M., & Liu, Y. (2018) · Advanced Biomedical and Clinical Diagnostic and Surgical Guidance Systems · doi:10.1117/12.2300089 · Cited by 2 · see citing works
Self-citationRavi, P., Singh, S. P., Kang, J. W., Tran, S., Dasari, R. R., So, P. T. C., Liepmann, D., Katti, K. S., Katti, D. R., Renugopalakrishnan, V., et al. (2020) · Analytical Chemistry · doi:10.1021/acs.analchem.0c02401 · Cited by 1 · see citing works
Gold- or Silver-Nanoparticle SERS Platforms for Plasma-Based Diagnostics and AI-Driven Analysis
Elizur, G. L., Canhoto, A., Soares, G. E., Ferreira, L. S., Pereira, E., & Franco, R. (2026) · Sensors · doi:10.3390/s26134131 · Cited by 1 · see citing works
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Self-citationFiberoptics SERS sensors using plasmonic nanostar probes for detection of molecular biotargets
Cupil‐Garcia, V., Strobbia, P., Ran, Y., Crawford, B. M., Wang, H., Zentella, R., Sun, T., & Vo‐Dinh, T. (2020) · Plasmonics in Biology and Medicine · doi:10.1117/12.2552993 · Cited by 1 · see citing works
Self-citationLi, J. Q., & Vo‐Dinh, T. (2022) · doi:10.1117/12.2617363 · Cited by 1 · see citing works
Self-citation
- Authors
- Wang, H.-N., Crawford, B. M., Fales, A. M., Bowie, M. L., Seewaldt, V. L., & Vo-Dinh, T.
- Affiliations
- Duke University (US)
- Department of Biomedical Engineering, ‡Fitzpatrick Institute for Photonics, and ⊥Department of Chemistry, Duke University, Durham, North Carolina 27708, United States
- Venue
- The Journal of Physical Chemistry C
- Publisher
- American Chemical Society (ACS)
- Published
- 2016-07-11
- Volume
- 120
- Issue
- 37
- Pages
- 21047-21055
- ISSN
- 1932-7447 (ISSN-L)
- 1932-7455
- PMC
- PMC5645027
- OpenAlex
- W2468826163
- Cited by
- 124
- References
- 57
- Citations by year
- 2026: 2 · 2025: 1 · 2024: 6 · 2023: 10 · 2022: 15 · 2021: 14 · 2020: 18 · 2019: 26 · 2018: 18 · 2017: 14
- FWCI
- 10.05
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- The Journal of Physical Chemistry C (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Cancer Institute (1 R21 CA196426)
- Office of Science (DE-SC0014077)
- Duke Faculty Exploratory Research Fund
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Advanced biosensing and bioanalysis techniques
- Physical Sciences › Materials Science › Electronic, Optical and Magnetic Materials › Gold and Silver Nanoparticles Synthesis and Applications
- Health Sciences › Medicine › Infectious Diseases › SARS-CoV-2 detection and testing
- Keywords
- microRNA detection, surface-enhanced Raman scattering, multiplexed biomarker detection, miR-21, miR-34a, breast cancer biomarkers, small RNA
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