Sensitive surface enhanced Raman scattering multiplexed detection of matrix metalloproteinase 2 and 7 cancer markers

A surface enhanced Raman spectroscopy (SERS) based platform was developed for sensitive multiplexed detection of matrix metalloproteinases (MMP) (MMP-2 and MMP-7) with low limit of detection and high specificity. Detection is based on the virtue of enzymatic reaction where a peptide can be cleaved o...

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Main Authors: Gong, Tianxun, Kong, Kien Voon, Goh, Douglas, Olivo, Malini, Yong, Ken-Tye
Other Authors: School of Electrical and Electronic Engineering
Format: Journal Article
Language:English
Published: 2016
Subjects:
Online Access:https://hdl.handle.net/10356/82872
http://hdl.handle.net/10220/40384
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author Gong, Tianxun
Kong, Kien Voon
Goh, Douglas
Olivo, Malini
Yong, Ken-Tye
author2 School of Electrical and Electronic Engineering
author_facet School of Electrical and Electronic Engineering
Gong, Tianxun
Kong, Kien Voon
Goh, Douglas
Olivo, Malini
Yong, Ken-Tye
author_sort Gong, Tianxun
collection NTU
description A surface enhanced Raman spectroscopy (SERS) based platform was developed for sensitive multiplexed detection of matrix metalloproteinases (MMP) (MMP-2 and MMP-7) with low limit of detection and high specificity. Detection is based on the virtue of enzymatic reaction where a peptide can be cleaved only by its corresponding enzyme. The platform comprises two components, a specialized SERS-based bimetallic-film-over-nanosphere (BMFON) substrate and gold nanoparticles (AuNPs). The two components were functionalized such that binding between the two would occur through biotin-avidin-biotin complexation. Binding is hindered by MMP peptide chains conjugated onto the surfaces of the substrate and AuNPs, and can be removed only by cleaving the peptide chains with corresponding enzymes. Since AuNP binding sites become free after the peptides are cleaved, the number of binding sites for AuNPs onto the substrate would increase. By tagging the AuNPs, concentrations of MMP-specific enzymes can be quantified through examining intensities of signature SERS peaks of the tags. This cleave-and-bind mechanism was first validated by individual detection and quantification of MMP-2 and MMP-7. The platform was demonstrated to be able to sensitively detect concentrations of specific enzymes ranging from 1 ng/mL to 40 μg/mL, with close correlation between SERS intensity and concentrations. Finally, the multiplexed detection of MMP-2 and MMP-7 was demonstrated. The multiplexity of this platform provides a robust way to analyze diseases associated with MMP-2 and MMP-7 enzymes. Our work can be further developed as a clinical diagnostic tool to detect other MMP proteinase in bio-fluids samples, widening the number of biomarkers needed to characterize diseases better
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spelling ntu-10356/828722022-02-16T16:30:36Z Sensitive surface enhanced Raman scattering multiplexed detection of matrix metalloproteinase 2 and 7 cancer markers Gong, Tianxun Kong, Kien Voon Goh, Douglas Olivo, Malini Yong, Ken-Tye School of Electrical and Electronic Engineering Medical optics A surface enhanced Raman spectroscopy (SERS) based platform was developed for sensitive multiplexed detection of matrix metalloproteinases (MMP) (MMP-2 and MMP-7) with low limit of detection and high specificity. Detection is based on the virtue of enzymatic reaction where a peptide can be cleaved only by its corresponding enzyme. The platform comprises two components, a specialized SERS-based bimetallic-film-over-nanosphere (BMFON) substrate and gold nanoparticles (AuNPs). The two components were functionalized such that binding between the two would occur through biotin-avidin-biotin complexation. Binding is hindered by MMP peptide chains conjugated onto the surfaces of the substrate and AuNPs, and can be removed only by cleaving the peptide chains with corresponding enzymes. Since AuNP binding sites become free after the peptides are cleaved, the number of binding sites for AuNPs onto the substrate would increase. By tagging the AuNPs, concentrations of MMP-specific enzymes can be quantified through examining intensities of signature SERS peaks of the tags. This cleave-and-bind mechanism was first validated by individual detection and quantification of MMP-2 and MMP-7. The platform was demonstrated to be able to sensitively detect concentrations of specific enzymes ranging from 1 ng/mL to 40 μg/mL, with close correlation between SERS intensity and concentrations. Finally, the multiplexed detection of MMP-2 and MMP-7 was demonstrated. The multiplexity of this platform provides a robust way to analyze diseases associated with MMP-2 and MMP-7 enzymes. Our work can be further developed as a clinical diagnostic tool to detect other MMP proteinase in bio-fluids samples, widening the number of biomarkers needed to characterize diseases better ASTAR (Agency for Sci., Tech. and Research, S’pore) Accepted version 2016-04-08T02:46:43Z 2019-12-06T15:07:20Z 2016-04-08T02:46:43Z 2019-12-06T15:07:20Z 2015 Journal Article Gong, T., Kong, K. V., Goh, D., Olivo, M., & Yong, K.-T. (2015). Sensitive surface enhanced Raman scattering multiplexed detection of matrix metalloproteinase 2 and 7 cancer markers. Biomedical Optics Express, 6(6), 2076-2087. 2156-7085 https://hdl.handle.net/10356/82872 http://hdl.handle.net/10220/40384 10.1364/BOE.6.002076 26114030 en Biomedical Optics Express © 2015 Optical Society of America. This is the author created version of a work that has been peer reviewed and accepted for publication by Biomedical Optics Express, Optical Society of America. It incorporates referee’s comments but changes resulting from the publishing process, such as copyediting, structural formatting, may not be reflected in this document. The published version is available at: [http://dx.doi.org/10.1364/BOE.6.002076]. 12 p. application/pdf
spellingShingle Medical optics
Gong, Tianxun
Kong, Kien Voon
Goh, Douglas
Olivo, Malini
Yong, Ken-Tye
Sensitive surface enhanced Raman scattering multiplexed detection of matrix metalloproteinase 2 and 7 cancer markers
title Sensitive surface enhanced Raman scattering multiplexed detection of matrix metalloproteinase 2 and 7 cancer markers
title_full Sensitive surface enhanced Raman scattering multiplexed detection of matrix metalloproteinase 2 and 7 cancer markers
title_fullStr Sensitive surface enhanced Raman scattering multiplexed detection of matrix metalloproteinase 2 and 7 cancer markers
title_full_unstemmed Sensitive surface enhanced Raman scattering multiplexed detection of matrix metalloproteinase 2 and 7 cancer markers
title_short Sensitive surface enhanced Raman scattering multiplexed detection of matrix metalloproteinase 2 and 7 cancer markers
title_sort sensitive surface enhanced raman scattering multiplexed detection of matrix metalloproteinase 2 and 7 cancer markers
topic Medical optics
url https://hdl.handle.net/10356/82872
http://hdl.handle.net/10220/40384
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