Analytical and Bioanalytical Chemistry

, Volume 411, Issue 20, pp 5149–5157 | Cite as

Dopamine-functionalized cyclodextrins: modification of reduced graphene oxide based electrodes and sensing of folic acid in human serum

  • Fereshteh ChekinEmail author
  • Vladyslav Mishyn
  • Alexandre Barras
  • Joel Lyskawa
  • Ran Ye
  • Sorin Melinte
  • Patrice Woisel
  • Rabah Boukherroub
  • Sabine SzuneritsEmail author
Research Paper


A mandatory step in any sensor fabrication is the introduction of analyte-specific recognition elements to the transducer surface. In this study, the possibility to anchor β-cyclodextrin-modified dopamine to a reduced graphene oxide based electrochemical transducer for the sensitive and selective sensing of folic acid is demonstrated. The sensor displays good electrocatalytic activity toward the oxidation of folic acid. The strong affinity of the surface-confined β-cyclodextrin for folic acid, together with favorable electron transfer characteristics, resulted in a sensor with a detection limit of 1 nM for folic acid and a linear response up to 10 μM. Testing of the sensor on serum samples from healthy individuals and patients diagnosed with folic acid deficiency validated the sensing capability.

Graphical abstract


β-Cyclodextrin Reduced graphene oxide Electrophoretic deposition Folic acid Electrochemical sensor 



Financial support from the Centre National de la Recherche Scientifique, the University of Lille, the Hauts-de-France region, the CPER “Photonics for Society,” and the Agence Nationale de la Recherche through the FLAG-ERA JTC 2015-Graphtivity project is acknowledged. We are grateful to the Walloon Region for financial support in the frame of the "BATWAL" project - "Programme d'Excellence". Work at UCLouvain has been carried out within the project LUMINOPTEX (avec le soutien du Fonds Européen de Développement Régional / met steun van het Europees Fonds voor Regionale Ontwikkeling - INTERREG V France-Wallonie-Vlaanderen). The work was supported by the Belgian F.R.S. - FNRS in the frame of the research conventions no. R 50.02.16.F and no. T.0106.16.

Compliance with ethical standards

Conflict of interest

The authors declare that they have no competing interests.

Supplementary material

216_2019_1892_MOESM1_ESM.pdf (147 kb)
ESM 1 (PDF 146 kb)


  1. 1.
    Ambrosi A, Chua CK, Latiff NM, Loo AH, Wong CHA, Eng AYS, et al. Graphene and its electrochemistry - an update. Chem Soc Rev. 2016;45:2458–93.CrossRefGoogle Scholar
  2. 2.
    Szunerits S, Boukherroub R. Graphene-based bioelectrochemistry and bioelectronics: a concept for the future? Curr Opin Electrochem. 2018;12:141–7.CrossRefGoogle Scholar
  3. 3.
    Szunerits S, Boukherroub R. Graphene-based nanomaterials in innovative electrochemistry. Curr Opin Electrochem. 2018;10:24–30.CrossRefGoogle Scholar
  4. 4.
    Jijie R, Kahlouche K, Barras A, Bouckaert J, Tijani Gharbi T, Szunerits S, et al. Reduced graphene oxide/polyethylenimine based immunosensor for the selective and sensitive electrochemical detection of uropathogenic Escherichia coli. Sensors Actuators B Chem. 2018;260:255–63.CrossRefGoogle Scholar
  5. 5.
    Kahlouche K;R, Jijie IH, Barras A, Gharbi T, Yahiaoui R, Herlem G, et al. Controlled modification of electrochemical microsystems with polyethylenimine/reduced graphene oxide using electrophoretic deposition: sensing of dopamine levels in meat samples. Talanta. 2018;178:432–40.CrossRefGoogle Scholar
  6. 6.
    Kaminska I, Barras A, Coffinier Y, Lisowski W, Niedziolka-Jonsson J, Woisel P, et al. Preparation of a responsive carbohydrate-coated biointerface based on graphene/azido-terminated tetrathiafulvalene nanohybrid material. ACS Appl Mater Interfaces. 2012;4:5386.CrossRefGoogle Scholar
  7. 7.
    Kaminska I, Das MR, Coffinier Y, Niedziolka-Jonsson J, Woisel P, Opallo M, et al. Preparation of graphene/tetrathiafulvalene nanocomposite switchable surfaces. Chem Commun. 2012;48:1221.CrossRefGoogle Scholar
  8. 8.
    Xu LQ, Yang WJ, Neoh K-G, Kang E-T, Fu GD. Dopamine-induced reduction and functionalization of graphene oxide nanosheets. Macromolecules. 2010;48:8336.CrossRefGoogle Scholar
  9. 9.
    Kaminska I, Das MR, Coffinier Y, Niedziolka-Jonsson J, Sobczak J, Woisel P, et al. Reduction and functionalization of graphene oxide sheets using biomimetic dopamine derivatives in one step. ACS Appl Mater Interfaces. 2012;4:1016.CrossRefGoogle Scholar
  10. 10.
    Szejtli J. Introduction and general overview of cyclodextrin chemistry. Chem Rev. 1998;98:1743–54.CrossRefGoogle Scholar
  11. 11.
    Yu G, Jie K, Huang F. Supramolecular amphiphiles based on host-guest molecular recognition motifs. Chem Rev. 2015;115:7240–303.CrossRefGoogle Scholar
  12. 12.
    Fritea L, Le Goff A, Putaux J-L, Tertis M, Cristea C, Săndulescu R, et al. Design of a reduced-graphene-oxide composite electrode from an elctropolymerizable graphene aqueous dispersion using a cyclodextrin-pyrrole monomer. Application to dopamine biosensing. Electrochim Acta. 2015;178:108–12.CrossRefGoogle Scholar
  13. 13.
    Harley CC, Rooney AD, Breslin CB. The selective detection of dopamine at a polypyrrole film doped with sulfonated β-cyclodextrins. Sensors Actuators B Chem. 2010;150:498–504.CrossRefGoogle Scholar
  14. 14.
    Tian X. Simultaneous determination of l-ascorbic acid, dopamine and uric acid with gold nanoparticles-β-cyclodextrin-graphene-modified electrode by square wave voltammetry. Talanta. 2012;93:79–85.CrossRefGoogle Scholar
  15. 15.
    Wen D, Liu W, Herrmann A-K, Haubold D, Holzschuh M, Simon F, et al. Simple and sensitive colorimetric detection of dopamine based on assembly of cyclodextrin-modified Au nanoparticles. Small. 2016;12:2439–42.CrossRefGoogle Scholar
  16. 16.
    Wu Y, Dou Z, Liu Y, Lv G, Pua T, He X. Dopamine sensor development based on the modification of glassy carbon electrode with β-cyclodextrin-poly(N-isopropylacrylamide). RSC Adv. 2013;3:12726–34.CrossRefGoogle Scholar
  17. 17.
    Subhadeep S, Aditi R, Kanak R, Mahendra NR. Study to explore the mechanism to form inclusion complexes of β-cyclodextrin with vitamin molecules. Sci Rep. 2016;6:35764.CrossRefGoogle Scholar
  18. 18.
    Liang W, Rong Y, Fan L, Dong W, Dong Q, Yang C, et al. 3D graphene/hydroxypropyl-β-cyclodextrin nanocomposite as an electrochemical chiral sensor for the recognition of tryptophan enantiomers. J Mater Chem C. 2018;6:12822–9.CrossRefGoogle Scholar
  19. 19.
    Tao Y, Dai J, Kong Y, Sha Y. Temperature-sensitive electrochemical recognition of tryptophan enantiomers based on β-cyclodextrin self-assembled on poly(l-glutamic acid). Anal Chem. 2014;86:2633–9.CrossRefGoogle Scholar
  20. 20.
    Mukdasai S, Poosittisak S, Ngeontae W, Srijaranai S. A highly sensitive electrochemical determination of l-tryptophan in the presence of ascorbic acid and uric acid using in situ addition of tetrabutylammonium bromide on the ß-cyclodextrin incorporated multi-walled carbon nanotubes modified electrode. Sensors Actuators B Chem. 2018;272:518–25.CrossRefGoogle Scholar
  21. 21.
    Du D, Wang M, Cai J, Zhang A. Sensitive acetylcholinesterase biosensor based on assembly of β-cyclodextrins onto multiwall carbon nanotubes for detection of organophosphates pesticides. Sensors Actuators B Chem. 2010;146:337–41.CrossRefGoogle Scholar
  22. 22.
    Khaled E, Kamel MS, Hassan HN, Haroun AA, Youssef AM, Aboul-Enein HY. Novel multi walled carbon nanotubes/β-cyclodextrin based carbon paste electrode for flow injection potentiometric determination of piroxicam. Talanta. 2012;97:96–102.CrossRefGoogle Scholar
  23. 23.
    Alarcon-Angeles G, Pérez-López B, Palomar-Pardave M, Ramírez-Silva MT, Alegret S, Merkoçi A. Enhanced host–guest electrochemical recognition of dopamine using cyclodextrin in the presence of carbon nanotubes. Carbon. 2008;49:898.CrossRefGoogle Scholar
  24. 24.
    Tan L, Zhou K-G, Zhang Y-H, Wang H-X, Wang X-D, Guo Y-F, et al. Nanomolar detection of dopamine in the presence of ascorbic acid at β-cyclodextrin/graphene nanocomposite platform. Electrochem Commun. 2010;12:557.CrossRefGoogle Scholar
  25. 25.
    Institute of Medicine. Dietary reference intakes for thiamin, riboflavin, niacin, vitamin B6, folate, vitamin B12, pantothenic acid, biotin, and choline. Washington: National Academies Press; 1988. Scholar
  26. 26.
    Ren W, Fang Y, Wang E. A binary functional substrate for enrichment and ultrasensitive SERS spectroscopic detection of folic acid using graphene oxide/Ag nanoparticle hybrids. ACS Nano. 2011;5:6425–33.CrossRefGoogle Scholar
  27. 27.
    Breithaupt DE. Determination of folic acid by ion-pair RP-HPLC in vitamin-fortified fruit juices after solid-phase extraction. Food Chem. 2001;74:521–5.CrossRefGoogle Scholar
  28. 28.
    Combs GF, McClung JP. The vitamins: fundamental aspects in nutrition and health. San Diego: Academic; 2017.Google Scholar
  29. 29.
    Sanchez H. High levels of circulating folate concentrations are associated with DNA methylation of tumor suppressor and repair genes p16, MLH1, and MGMT in elderly Chileans. Clin Epigenetics. 2017;9:74.CrossRefGoogle Scholar
  30. 30.
    Zayed A, Bustami R, Alabsi W, El-Elimat T. Development and validation of a rapid high-performance liquid chromatography–tandem mass spectrometric method for determination of folic acid in human plasma. Pharmaceuticals. 2018;11:52.CrossRefGoogle Scholar
  31. 31.
    Abdelwahab AA, Shim YB. Simultaneous determination of ascorbic acid, dopamine, uric acid and folic acid based on activated graphene/MWCNT nanocomposite loaded Au nanoclusters. Sensors Actuators B Chem. 2015;221:659–65.CrossRefGoogle Scholar
  32. 32.
    Akbar S, Anwar A, Kanwal Q. Electrochemical determination of folic acid: a short review. Anal Biochem. 2016;510:98–105.CrossRefGoogle Scholar
  33. 33.
    Babakhanian A, Kaki S, Ahmadi M, Ehzari H, Pashabadi A. Development of α-polyoxometalate–polypyrrole–Au nanoparticles modified sensor applied for detection of folic acid. Biosens Bioelectron. 2014;60:185–90.CrossRefGoogle Scholar
  34. 34.
    Chekin F, Teodorescu F, Coffinier Y, Pan GH, Barras A, Boukherroub R, et al. MoS2/reduced graphene oxide as active hybrid material for the electrochemical detection of folic acid in human serum. Biosens Bioelectron. 2016;85:807–13.CrossRefGoogle Scholar
  35. 35.
    Kalimuthu P, John SA. Selective electrochemical sensor for folic acid at physiological pH using ultrathin electropolymerized film of functionalized thiadiazole modified glassy carbon electrode. Biosens Bioelectron. 2009;24:3575–80.CrossRefGoogle Scholar
  36. 36.
    Lavanya N, Fazio E, Neri F, Bonavita A, Leonardi SG, Neri G, et al. Electrochemical sensor for simultaneous determination of ascorbic acid, uric acid and folic acid based on Mn-SnO2 nanoparticles modified glassy carbon electrode. J Electroanal Chem. 2016;770:23–32.CrossRefGoogle Scholar
  37. 37.
    Mazloum-Ardakani M, Beitollahi H, Amini MK, Mirkhalaf F, Abdollahi-Alibeik M. New strategy for simultaneous and selective voltammetric determination of norepinephrine, acetaminophen and folic acid using ZrO2 nanoparticles-modified carbon paste electrode. Sensors Actuators B Chem. 2010;151:243–9.CrossRefGoogle Scholar
  38. 38.
    Prasad BB, Madhuri R, Tiwari MP, Sharma PS. Electrochemical sensor for folic acid based on a hyperbranched molecularly imprinted polymer-immobilized sol–gel-modified pencil graphite electrode. Sensors Actuators B Chem. 2010;146:321–30.CrossRefGoogle Scholar
  39. 39.
    Barras A, Szunerits S, Marcon L, Monfilliette-Dupont N, Boukherroub R. Functionalization of diamond nanoparticles using “click” chemistry. Langmuir. 2010;26:13168–72.CrossRefGoogle Scholar
  40. 40.
    Kaminska I, Qi W, Barras A, Sobczak J, Niedziolka-Jonsson J, Woisel P, et al. Thiol-yne click reactions on alkynyl-dopamine-modified reduced graphene oxide. Chem Eur J. 2013;19:8673–8.CrossRefGoogle Scholar
  41. 41.
    Thorbjørn Terndrup N, Wintgens V, Amiel C, Wimmer R, Lambertsen Larsen K. Facile synthesis of β-cyclodextrin-dextran polymers by “click” chemistry. Biomacromolecules. 2010;11:1710–5.CrossRefGoogle Scholar
  42. 42.
    Chavez-Valdez A, Shaffer MSP, Boccaccini AR. Applications of graphene electrophoretic deposition. a review. J Phys Chem B. 2013;117:1502–15.CrossRefGoogle Scholar
  43. 43.
    Wang Q, Vasilescu A, Wang Q, Coffinier Y, Li M, Boukherroub R, et al. Electrophoretic approach for the simultaneous deposition and functionalization of reduced graphene oxide nanosheets with diazonium compounds: application for lysozyme sensing in serum. ACS Appl Mater Interfaces. 2017;9:12823–31.CrossRefGoogle Scholar
  44. 44.
    Palomar-Pardavé M, Alarcón-Ángeles G, Ramírez-Silva MT, Romero-Romo M, Rojas-Hernández A, Corona-Avendaño S. Electrochemical and spectrophotometric determination of the formation constants of the ascorbic acid-β-cyclodextrin and dopamine-β-cyclodextrin inclusion complexes. J Incl Phenom Macrocycl Chem. 2011;69:91–9.CrossRefGoogle Scholar
  45. 45.
    Arvinte A, Marangoci N, Nicolescu A, Pintala M. Electrochemical evidence for inclusion complexes of thiotriazinone with cyclodextrins. RSC Adv. 2016;6:82817.CrossRefGoogle Scholar
  46. 46.
    Guzman-Hernandez DS, Palmar-Pardavé M, Rojas-Hernandez A, Corona-Avendano S, Romero-Rom M, Ramirez-Silva MT. Electrochemical quantification of the thermodynamic equilibrium constant of the tenoxicam-β-cyclodextrin inclusion complex formed on the surface of a poly-β-cyclodextrin-modified carbon past electrode. Electrochim Acta. 2014;140:535–40.CrossRefGoogle Scholar
  47. 47.
    Fragoso A, Almill E, Cao R, Echegoyen L, Gonzalez-Jonte R. A supramolecular approach to the selective detection of dopamine in the presence of ascorbate. Chem Commun. 2004;5:2230.Google Scholar
  48. 48.
    Kinesley MP, Desai PB, Srivastava AK. Simultaneous electro-catalytic oxidative determination of ascorbic acid and folic acid using Fe3O4 nanoparticles modified carbon paste electrode. J Electroanal Chem. 2015;741:71–9.CrossRefGoogle Scholar
  49. 49.
    Wang Z, Han Q, Xia J, Xia L, Bi S, Shi G, et al. A novel phosphomolybdic acid–polypyrrole/graphene composite modified electrode for sensitive determination of folic acid. J Electroanal Chem. 2014;726:107–11.CrossRefGoogle Scholar
  50. 50.
    Ceborska M, Zimnicka M, Wszelaka-Rylik M, Tro A. Characterization of folic acid/native cyclodextrins host–guest complexes in solution. J Mol Struct. 2016;1109:114.CrossRefGoogle Scholar

Copyright information

© Springer-Verlag GmbH Germany, part of Springer Nature 2019

Authors and Affiliations

  • Fereshteh Chekin
    • 1
    • 2
    Email author
  • Vladyslav Mishyn
    • 2
  • Alexandre Barras
    • 2
  • Joel Lyskawa
    • 3
  • Ran Ye
    • 4
  • Sorin Melinte
    • 4
  • Patrice Woisel
    • 3
  • Rabah Boukherroub
    • 2
  • Sabine Szunerits
    • 2
    Email author
  1. 1.Department of Chemistry, Ayatollah Amoli BranchIslamic Azad UniversityAmolIran
  2. 2.Université de Lille, CNRS, Centrale Lille, ISENUniversité de ValenciennesLilleFrance
  3. 3.Unité des Matériaux et Transformations (UMR 8207), Equipe Ingénierie des Systèmes PolymèresUniversité de LilleVilleneuve d’Ascq CedexFrance
  4. 4.Institute of Information and Communication Technologies, Electronics and Applied MathematicsUniversité catholique de LouvainLouvain-la-NeuveBelgium

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