Abstract
A selective fluorescence turn-on immunosensor for the specific detection of cardiac troponin I (cTnI), the potent biomarker for myocardial infarction diagnosis, was developed with a nano couple comprised of protein-stabilized gold nanocluster and gold nanoparticle. The red fluorescence of cTnI-specific antibody tagged bovine serum albumin stabilized gold nanoclusters was quenched with gold nanoparticles (AuNP) via the intensive interaction between amine and hydroxyl functionalities of BSA and AuNP. Through this, the adsorption of gold nanoclusters at the surface of AuNP, resulting in a core-satellite assembly, was assumed to quench the fluorescence emission. While in the presence of cTnI antigen, this gets disturbed due to the formation of immunocomplex between cTnI antigen and antibody, which restricts the close interaction between gold clusters and nanoparticles, thereby restoring quenched fluorescence. The enhancement in fluorescence signal is directly related to the concentration of cTnI, and this facilitates the selective detection of cTnI in the linear concentration range 0.7 to 10 ng/mL without any interference from other potentially interfering co-existing biomolecules. An appreciable limit of detection of 0.51 ng/mL and a limit of quantification of 0.917 ng/mL for cTnI is comparable to that of the previous report.
Graphical Abstract
Similar content being viewed by others
Data availability
Not applicable.
References
Cardiovascular diseases (CVDs), (n.d.) https://www.who.int/news-room/fact-sheets/detail/cardiovascular-diseases-(cvds) (accessed May 2, 2023)
Qureshi A, Gurbuz Y, Niazi JH (2012) Biosensors for cardiac biomarkers detection: a review. Sens Actuators B Chem 171–172:62–76. https://doi.org/10.1016/j.snb.2012.05.077
Han X, Li S, Peng Z, Othman AM, Leblanc R (2016) Recent development of cardiac troponin I detection. ACS Sens 1:106–114. https://doi.org/10.1021/acssensors.5b00318
Zhu L, Ye J, Yan M, Zhu Q, Wang S, Huang J, Yang X (2019) Electrochemiluminescence immunosensor based on Au nanocluster and hybridization chain reaction signal amplification for ultrasensitive detection of cardiac troponin I. ACS Sens 4:2778–2785. https://doi.org/10.1021/acssensors.9b01369
Raj V, Alex S (2021) Non-enzymatic colorimetric sensor for cardiac troponin I (cTnI) based on self-assembly of gold nanorods on heparin. Gold Bull 54:1–7. https://doi.org/10.1007/S13404-020-00287-W/METRICS
Shan M, Li M, Qiu X, Qi H, Gao Q, Zhang C (2014) Sensitive electrogenerated chemiluminescence peptide-based biosensor for the determination of troponin I with gold nanoparticles amplification. Gold Bull 47:57–64. https://doi.org/10.1007/S13404-013-0113-X/TABLES/1
Wu AHB, Apple FS, Gibler WB, Jesse RL, Warshaw MM, Valdes R (1999) National Academy of Clinical Biochemistry Standards of Laboratory Practice: recommendations for the use of cardiac markers in coronary artery diseases. Clin Chem 45:1104–1121. https://doi.org/10.1093/clinchem/45.7.1104
Chen G, Song F, Xiong X, Peng X (2013) Fluorescent nanosensors based on fluorescence resonance energy transfer (FRET). Ind Eng Chem Res 52:11228–11245. https://doi.org/10.1021/ie303485n
Halawa MI, Lai J, Xu G (2018) Gold nanoclusters: synthetic strategies and recent advances in fluorescent sensing. Mater Today Nano 3:9–27. https://doi.org/10.1016/J.MTNANO.2018.11.001
Zheng J, Nicovich PR, Dickson RM (2007) Highly fluorescent noble-metal quantum dots. Ann Rev Phys Chem 58:409–431. https://doi.org/10.1146/annurev.physchem.58.032806.104546
Qu X, Li Y, Li L, Wang Y, Liang J, Liang J (2015) Fluorescent gold nanoclusters: synthesis and recent biological application, J Nanomater 2015. https://doi.org/10.1155/2015/784097
Chen LY, Wang CW, Yuan Z, Chang HT (2015) Fluorescent gold nanoclusters: recent advances in sensing and imaging. Anal Chem 87:216–229. https://doi.org/10.1021/ac503636j
Li Y, Du Q, Zhang X, Cao H, Huang Y (2019) Kojic acid capped gold nanoclusters with aggregation-induced emission for fluorometric screening of the activity of alkaline phosphatase. Microchim Acta 186:1–8. https://doi.org/10.1007/S00604-019-3681-5/FIGURES/4
Chen J, Li Z, Ge J, Yang R, Zhang L, Qu LB, Wang HQ, Zhang L (2015) An aptamer-based signal-on bio-assay for sensitive and selective detection of Kanamycin A by using gold nanoparticles. Talanta 139:226–232. https://doi.org/10.1016/J.TALANTA.2015.02.036
Leng Y, Xie K, Ye L, Li G, Lu Z, He J (2015) Gold-nanoparticle-based colorimetric array for detection of dopamine in urine and serum. Talanta 139:89–95. https://doi.org/10.1016/J.TALANTA.2015.02.038
Chuang KT, Lin YW (2017) Microwave-assisted formation of gold nanoclusters capped in bovine serum albumin and exhibiting red or blue emission. J Phys Chem C 121:26997–27003. https://doi.org/10.1021/acs.jpcc.7b09349
Le Guével X, Hötzer B, Jung G, Hollemeyer K, Trouillet V, Schneider M (2011) Formation of fluorescent metal (Au, Ag) nanoclusters capped in bovine serum albumin followed by fluorescence and spectroscopy. J Phys Chem C 115:10955–10963. https://doi.org/10.1021/jp111820b
Xie J, Zheng Y, Ying JY (2009) Protein-directed synthesis of highly fluorescent gold nanoclusters. https://doi.org/10.1021/JA806804U
Bhatnagar D, Kumar V, Kumar A, Kaur I (2016) Graphene quantum dots FRET based sensor for early detection of heart attack in human. Biosens Bioelectron 79:495–499. https://doi.org/10.1016/j.bios.2015.12.083
Gogoi S, Khan R (2018) Fluorescence immunosensor for cardiac troponin T based on Förster resonance energy transfer (FRET) between carbon dot and MoS2 nano-couple. Phys Chem Chem Phys 20:16501–16509. https://doi.org/10.1039/c8cp02433b
Zheng J, Zhou C, Yu M, Liu J (2012) Different sized luminescent gold nanoparticles. Nanoscale 4:4073–4083. https://doi.org/10.1039/c2nr31192e
Bastús NG, Comenge J, Puntes V (2011) Kinetically controlled seeded growth synthesis of citrate-stabilized gold nanoparticles of up to 200 nm: size focusing versus Ostwald ripening. Langmuir 27:11098–11105. https://doi.org/10.1021/LA201938U/SUPPL_FILE/LA201938U_SI_001.PDF
Grys DB, De Nijs B, Salmon AR, Huang J, Wang W, Chen WH, Scherman OA, Baumberg JJ (2020) Citrate coordination and bridging of gold nanoparticles: the role of gold adatoms in AuNP aging. ACS Nano 14:8689–8696. https://doi.org/10.1021/ACSNANO.0C03050/ASSET/IMAGES/LARGE/NN0C03050_0004.JPEG
Elsutohy MM, Selo A, Chauhan VM, Tendler SJB, Aylott JW (2018) Enhanced distance-dependent fluorescence quenching using size tuneable core shell silica nanoparticles. RSC Adv 8:35840–35848. https://doi.org/10.1039/C8RA05929B
Lin CY, Liu CH, Tseng WL (2010) Fluorescein isothiocyanate-capped gold nanoparticles for fluorescent detection of reactive oxygen species based on thiol oxidation and their application for sensing glucose in serum. Anal Methods 2:1810–1815. https://doi.org/10.1039/c0ay00428f
Cumberland SL, Strouse GF (2002) Analysis of the nature of oxyanion adsorption on gold nanomaterial surfaces. Langmuir 18:269–276. https://doi.org/10.1021/la011278n
Liu X, Atwater M, Wang J, Huo Q (2007) Extinction coefficient of gold nanoparticles with different sizes and different capping ligands. Colloids Surf B Biointerfaces 58:3–7. https://doi.org/10.1016/j.colsurfb.2006.08.005
Estimating the concentration of nanoparticles from the particle size data - Chemistry LibreTexts (n.d.) https://chem.libretexts.org/Bookshelves/Analytical_Chemistry/Supplemental_Modules_(Analytical_Chemistry)/Analytical_Sciences_Digital_Library/Contextual_Modules/Optical_Properties_of_Gold_Nanoparticles/01_Investigation_of_Gold_Nanoparticles/05_Estimating_the_concentration_of_nanoparticles_from_the_particle_size_data (accessed April 12, 2023)
Leng Y, Jiang K, Zhang W, Wang Y (2017) Synthesis of gold nanoparticles from Au(I) ions that shuttle to solidify: application on the sensor array design. Langmuir 33:6398–6403. https://doi.org/10.1021/ACS.LANGMUIR.7B01150/SUPPL_FILE/LA7B01150_SI_001.PDF
Leng Y, Qu P, Wang A, Jiang K, Dong Y, Han P, Cheng J, Zhang L (2023) Fabrication of glass-based analytical devices by immobilizing nanomaterials on glass substrate with a fluorescent glue for the highly sensitive determination of mercury ions. Microchim Acta 190:1–8. https://doi.org/10.1007/S00604-023-05875-Z/FIGURES/5
Govindaraju S, Ankireddy SR, Viswanath B, Kim J, Yun K (2017) Fluorescent gold nanoclusters for selective detection of dopamine in cerebrospinal fluid. Sci Rep 7. https://doi.org/10.1038/srep40298
Lillo CR, Calienni MN, Rivas Aiello B, Prieto MJ, Rodriguez Sartori D, Tuninetti J, Toledo P, del V. Alonso S, Moya S, Gonzalez MC, Montanari J, Soler-Illia GJAA (2020) BSA-capped gold nanoclusters as potential theragnostic for skin diseases: photoactivation, skin penetration, in vitro, and in vivo toxicity. Mater Sci Eng C Mater Biol Appl 112. https://doi.org/10.1016/J.MSEC.2020.110891
Medda L, Monduzzi M, Salis A (2015) The molecular motion of bovine serum albumin under physiological conditions is ion specific. Chem Commun 51:6663–6666. https://doi.org/10.1039/c5cc01538c
Fehér B, Lyngsø J, Bartók B, Mihály J, Varga Z, Mészáros R, Pedersen JS, Bóta A, Varga I (2020) Effect of pH on the conformation of bovine serum albumin - gold bioconjugates, J Mol Liq. 309. https://doi.org/10.1016/j.molliq.2020.113065
Nebu J, Anjali Devi JS, Aparna RS, Aswathy B, Aswathy AO, Sony G (2018) Fluorometric determination of morphine via its effect on the quenching of fluorescein by gold nanoparticles through a surface energy transfer process. Microchimica Acta 185. https://doi.org/10.1007/s00604-018-3050-9
Ghosh D, Chattopadhyay N (2015) Gold and silver nanoparticles based superquenching of fluorescence: a review. J Lumin 160:223–232. https://doi.org/10.1016/j.jlumin.2014.12.018
Qin H, Ma D, Du J (2018) Distance dependent fluorescence quenching and enhancement of gold nanoclusters by gold nanoparticles. Spectrochim Acta A Mol Biomol Spectrosc 189:161–166. https://doi.org/10.1016/j.saa.2017.08.025
Posokhov YO, Kyrychenko A, Ladokhin AS (2010) Steady-state and time-resolved fluorescence quenching with transition metal ions as short-distance probes for protein conformation. Anal Biochem 407:284–286. https://doi.org/10.1016/J.AB.2010.07.035
Oh E, Huston AL, Shabaev A, Efros A, Currie M, Susumu K, Bussmann K, Goswami R, Fatemi FK, Medintz IL (2016) Energy transfer sensitization of luminescent gold nanoclusters: more than just the classical Förster mechanism. Sci Rep 6. https://doi.org/10.1038/srep35538
Yang X, Zhuo Y, Zhu S, Luo Y, Feng Y, Xu Y (2015) Selectively assaying CEA based on a creative strategy of gold nanoparticles enhancing silver nanoclusters’ fluorescence. Biosens Bioelectron 64:345–351. https://doi.org/10.1016/J.BIOS.2014.09.029
Chen C, Hildebrandt N (2020) Resonance energy transfer to gold nanoparticles: NSET defeats FRET. TrAC, Trends Anal Chem 123:115748. https://doi.org/10.1016/J.TRAC.2019.115748
Chen C, Midelet C, Bhuckory S, Hildebrandt N, Werts MHV (2018) ‡ † Nanobiophotonics, nanosurface energy transfer from long-lifetime terbium donors to gold nanoparticles. J Phys Chem C 122:2023. https://doi.org/10.1021/acs.jpcc.8b06539
Acknowledgements
The authors are grateful to the Head, Department of Chemistry, University of Kerala for the support, laboratory, and instrumental facilities offered. We also express our thanks to Director, Advanced Research Laboratory for Molecular Sensing and Imaging (State plan fund, 2020-21, Govt. of Kerala). We also thank the Director, Advanced Research Laboratory for Molecular Sensing and Imaging (State Plan Fund 2020- 21, Govt. of Kerala), Department of Chemistry, University of Kerala, Kariavattom, The Head, Department of Optoelectronics, University of Kerala and The Director, STIC, CUSAT, Kochi, Kerala, for the sophisticated instrumental analysis provided.
Author information
Authors and Affiliations
Corresponding author
Ethics declarations
Ethical approval
The work has been done in accordance with the recommendations of the Indian Council of Medical Research (ICMR) and the Human Ethical Committee of the University of Kerala. The university-level ethical clearance number is ULECRIHS/UOK/2019/ 48.
Conflict of interest
The authors declare no competing interests.
Additional information
Publisher's Note
Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.
Supplementary Information
Below is the link to the electronic supplementary material.
Rights and permissions
Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.
About this article
Cite this article
Anju, S.M., Merin, K.A., Varghese, S. et al. Antibody-functionalized gold nanoclusters/gold nanoparticle platform for the fluorescence turn-on detection of cardiac troponin I. Microchim Acta 191, 124 (2024). https://doi.org/10.1007/s00604-024-06194-7
Received:
Accepted:
Published:
DOI: https://doi.org/10.1007/s00604-024-06194-7