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CuO/Cu-MOF nanocomposite for highly sensitive detection of nitric oxide released from living cells using an electrochemical microfluidic device

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Abstract

The integration of large surface area and high catalytic profiles of Cu-MOF and CuO nanoparticles is described toward electrochemical sensing of nitric oxide (NO) in a microfluidic platform. The CuO/Cu-MOF nanocomposite was prepared through hydrothermal method, and its formation was confirmed by scanning electron microscopy (SEM), transmission electron microscopy (TEM), X-ray powder diffraction (XRD), X-ray photoelectron spectroscopy (XPS), and energy-dispersive X-ray spectroscopy (EDS). The CuO/Cu-MOF nanostructured modified Au electrodes enabled electrocatalytic NO oxidation at 0.6 V vs. reference electrode, demonstrating linear response over a broad concentration range of 0.03–1 μM and 1–500 μM with a detection limit of 7.8 nM. The interference effect of organic molecules and common ions was negligible, and the sensing system demonstrated excellent stability. Finally, an electrochemical microfluidic NO sensor was developed to detect of NO released from cancer cells, which were stimulated by L-arginine. Furthermore, in the presence of Fe3+, the stressed cells produced more NO. This work offers considerable potential for its practical applications in clinical diagnostics through determination of chemical symptoms in microliter-volume biological samples.

Graphical abstract

Electrochemical microfluidic NO sensor was developed for detection of NO released from cancer cells. This miniaturized device consumes less materials and provides the basis for greener analytical chemistry.

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References

  1. Dai Z, Tian L, Song B, Liu X, Yuan J (2017) Development of a novel lysosome-targetable time-gated luminescence probe for ratiometric and luminescence lifetime detection of nitric oxide in vivo. Chem Sci 8(3):1969–1976

    Article  CAS  PubMed  Google Scholar 

  2. Jia S, Fei J, Zhou J, Chen X, Meng J (2009) Direct electrochemistry of hemoglobin entrapped in cyanoethyl cellulose film and its electrocatalysis to nitric oxide. Biosens Bioelectron 24(10):3049–3054

    Article  CAS  PubMed  Google Scholar 

  3. Pluth MD, Tomat E, Lippard SJ (2011) Biochemistry of mobile zinc and nitric oxide revealed by fluorescent sensors. Annu Rev Biochem 80:333–355

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  4. Heales SJ, Bolaños JP, Stewart VC, Brookes PS, Land JM, Clark JB (1999) Nitric oxide, mitochondria and neurological disease. Biochimica et Biophysica Acta (BBA)-Bioenergetics 1410(2):215–228

    Article  CAS  Google Scholar 

  5. Hetrick EM, Schoenfisch MH (2009) Analytical chemistry of nitric oxide. Annu Rev Anal Chem 2:409–433

    Article  CAS  Google Scholar 

  6. Batchelor AM, Bartus K, Reynell C, Constantinou S, Halvey EJ, Held KF, Dostmann WR, Vernon J, Garthwaite J (2010) Exquisite sensitivity to subsecond, picomolar nitric oxide transients conferred on cells by guanylyl cyclase-coupled receptors. Proc Natl Acad Sci 107(51):22060–22065

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  7. Liu Y-L, Wang X-Y, Xu J-Q, Xiao C, Liu Y-H, Zhang X-W, Liu J-T, Huang W-H (2015) Functionalized graphene-based biomimetic microsensor interfacing with living cells to sensitively monitor nitric oxide release. Chem Sci 6(3):1853–1858

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  8. Bru M, Burguete MI, Galindo F, Luis SV, Marín MJ, Vigara L (2006) Cross-linked poly (2-hydroxyethylmethacrylate) films doped with 1, 2-diaminoanthraquinone (DAQ) as efficient materials for the colorimetric sensing of nitric oxide and nitrite anion. Tetrahedron Lett 47(11):1787–1791

    Article  CAS  Google Scholar 

  9. Kikuchi K, Nagano T, Hayakawa H, Hirata Y, Hirobe M (1993) Detection of nitric oxide production from a perfused organ by a luminol-hydrogen peroxide system. Anal Chem 65(13):1794–1799

    Article  CAS  PubMed  Google Scholar 

  10. Chen L, Wu D, Yoon J (2018) An ESIPT based fluorescence probe for ratiometric monitoring of nitric oxide. Sensors Actuators B Chem 259:347–353

    Article  CAS  Google Scholar 

  11. Everett SA, Dennis MF, Tozer GM, Prise VE, Wardman P, Stratford MR (1995) Nitric oxide in biological fluids: analysis of nitrite and nitrate by high-performance ion chromatography. J Chromatogr A 706(1–2):437–442

    Article  CAS  PubMed  Google Scholar 

  12. Mordvintcev P, Mülsch A, Busse R, Vanin A (1991) On-line detection of nitric oxide formation in liquid aqueous phase by electron paramagnetic resonance spectroscopy. Anal Biochem 199(1):142–146

    Article  CAS  PubMed  Google Scholar 

  13. Musameh MM, Dunn CJ, Uddin MH, Sutherland TD, Rapson TD (2018) Silk provides a new avenue for third generation biosensors: sensitive, selective and stable electrochemical detection of nitric oxide. Biosens Bioelectron 103:26–31

    Article  CAS  PubMed  Google Scholar 

  14. Yusoff N, Pandikumar A, Huang NM, Lim HN (2015) Facile synthesis of nanosized graphene/Nafion hybrid materials and their application in electrochemical sensing of nitric oxide. Anal Methods 7(8):3537–3544

    Article  CAS  Google Scholar 

  15. Bai RG, Muthoosamy K, Zhou M, Ashokkumar M, Huang NM, Manickam S (2017) Sonochemical and sustainable synthesis of graphene-gold (G-Au) nanocomposites for enzymeless and selective electrochemical detection of nitric oxide. Biosens Bioelectron 87:622–629

    Article  CAS  Google Scholar 

  16. Griveau S, Bedioui F (2013) Overview of significant examples of electrochemical sensor arrays designed for detection of nitric oxide and relevant species in a biological environment. Anal Bioanal Chem 405(11):3475–3488

    Article  CAS  PubMed  Google Scholar 

  17. Alizadeh N, Salimi A (2018) Ultrasensitive bioaffinity electrochemical sensors: advances and new perspectives. Electroanalysis 30(12):2803–2840

    Article  CAS  Google Scholar 

  18. Alizadeh N, Hallaj R, Salimi A (2018) Dual amplified electrochemical immunosensor for hepatitis B virus surface antigen detection using hemin/G-Quadruplex immobilized onto Fe3O4-AuNPs or (hemin-amino-rGO-au) nanohybrid. Electroanalysis 30(3):402–414

  19. Liu Z, Forsyth H, Khaper N, Chen A (2016) Sensitive electrochemical detection of nitric oxide based on AuPt and reduced graphene oxide nanocomposites. Analyst 141(13):4074–4083

    Article  CAS  PubMed  Google Scholar 

  20. Lang X-Y, Fu H-Y, Hou C, Han G-F, Yang P, Liu Y-B, Jiang Q (2013) Nanoporous gold supported cobalt oxide microelectrodes as high-performance electrochemical biosensors. Nat Commun 4:2169

    Article  PubMed  CAS  Google Scholar 

  21. Vilakazi SL, Nyokong T (2001) Voltammetric determination of nitric oxide on cobalt phthalocyanine modified microelectrodes. J Electroanal Chem 512(1–2):56–63

    Article  CAS  Google Scholar 

  22. Du F, Huang W, Shi Y, Wang Z, Cheng J (2008) Real-time monitoring of NO release from single cells using carbon fiber microdisk electrodes modified with single-walled carbon nanotubes. Biosens Bioelectron 24(3):415–421

    Article  CAS  PubMed  Google Scholar 

  23. Govindhan M, Chen A (2016) Enhanced electrochemical sensing of nitric oxide using a nanocomposite consisting of platinum-tungsten nanoparticles, reduced graphene oxide and an ionic liquid. Microchim Acta 183(11):2879–2887

    Article  CAS  Google Scholar 

  24. Mehmeti E, Stanković DM, Hajrizi A, Kalcher K (2016) The use of graphene nanoribbons as efficient electrochemical sensing material for nitrite determination. Talanta 159:34–39

    Article  CAS  PubMed  Google Scholar 

  25. Ananthi A, Phani KL (2016) Self-assembly of gold nanoparticles on sulphide functionalized polydopamine in application to electrocatalytic oxidation of nitric oxide. J Electroanal Chem 764:7–14

    Article  CAS  Google Scholar 

  26. Shahid MM, Rameshkumar P, Pandikumar A, Lim HN, Ng YH, Huang NM (2015) An electrochemical sensing platform based on a reduced graphene oxide–cobalt oxide nanocube@ platinum nanocomposite for nitric oxide detection. J Mater Chem A 3(27):14458–14468

    Article  CAS  Google Scholar 

  27. Adekunle AS, Lebogang S, Gwala PL, Tsele TP, Olasunkanmi LO, Esther FO, Boikanyo D, Mphuthi N, Oyekunle JA, Ogunfowokan AO (2015) Electrochemical response of nitrite and nitric oxide on graphene oxide nanoparticles doped with Prussian blue (PB) and Fe2O3 nanoparticles. RSC Adv 5(35):27759–27774

  28. Tan X, Yu C, Zhao C, Huang H, Yao X, Han X, Guo W, Cui S, Huang H, Qiu J (2019) Restructuring of Cu2O to Cu2O@ Cu-metal-organic framework for the selective electrochemical reduction of CO2. ACS Appl Mater Interfaces 11:9904–9910

  29. Zhang J-W, Zhang H-T, Du Z-Y, Wang X, Yu S-H, Jiang H-L (2014) Water-stable metal–organic frameworks with intrinsic peroxidase-like catalytic activity as a colorimetric biosensing platform. Chem Commun 50(9):1092–1094

    Article  CAS  Google Scholar 

  30. Herbst A, Janiak C (2017) MOF catalysts in biomass upgrading towards value-added fine chemicals. CrystEngComm 19(29):4092–4117

    Article  CAS  Google Scholar 

  31. Li H, Lv N, Li X, Liu B, Feng J, Ren X, Guo T, Chen D, Stoddart JF, Gref R (2017) Composite CD-MOF nanocrystals-containing microspheres for sustained drug delivery. Nanoscale 9(22):7454–7463

    Article  CAS  PubMed  Google Scholar 

  32. Amini S, Ebrahimzdeh H, Seidi S, Jalilian N (2020) Preparation of electrospun polyacrylonitrile/Ni-MOF-74 nanofibers for extraction of atenolol and captopril prior to HPLC-DAD. Microchim Acta 187(9):1–12

    Article  CAS  Google Scholar 

  33. Amini S, Ebrahimzadeh H, Seidi S, Jalilian N (2021) Preparation of Polyacrylonitrile/Ni-MOF electrospun nanofiber as an efficient fiber coating material for headspace solid-phase microextraction of diazinon and chlorpyrifos followed by CD-IMS analysis. Food Chem 350:129242

    Article  CAS  PubMed  Google Scholar 

  34. Alizadeh N, Salimi A, Hallaj R, Fathi F, Soleimani F (2018) Ni-hemin metal–organic framework with highly efficient peroxidase catalytic activity: toward colorimetric cancer cell detection and targeted therapeutics. Journal of nanobiotechnology 16(1):93

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  35. Du J-L, Zhang X-Y, Li C-P, Gao J-P, Hou J-X, Jing X, Mu Y-J, Li L-J (2018) A bi-functional luminescent Zn (II)-MOF for detection of nitroaromatic explosives and Fe3+ ions. Sensors Actuators B Chem 257:207–213

    Article  CAS  Google Scholar 

  36. Xu Y, Wu X-Q, Shen J-S, Zhang H-W (2015) Highly selective and sensitive recognition of histidine based on the oxidase-like activity of Cu2+ ions. RSC Adv 5(112):92114–92120

  37. Koel M, Kaljurand M (2019) Green analytical chemistry 2nd Edition, Royal society of Chemistry

  38. Alizadeh N, Ghasemi F, Salimi A, Hallaj R, Fathi F, Soleimani F (2020) Polymer nanocomposite film for dual colorimetric and fluorescent ascorbic acid detection integrated single-cell bioimaging with droplet microfluidic platform. Dyes Pigments 173:107875

    Article  CAS  Google Scholar 

  39. Alizadeh N, Salimi A (2019) Polymer dots as a novel probe for fluorescence sensing of dopamine and imaging in single living cell using droplet microfluidic platform. Anal Chim Acta 1091:40–49

    Article  CAS  PubMed  Google Scholar 

  40. Alizadeh N, Salimi A, Hallaj R (2018) Mimicking peroxidase activity of Co2(OH)2CO3-CeO2 nanocomposite for smartphone based detection of tumor marker using paper-based microfluidic immunodevice. Talanta 189:100–110

    Article  CAS  PubMed  Google Scholar 

  41. Li T-T, Qian J, Zheng Y-Q (2016) Facile synthesis of porous CuO polyhedron from Cu-based metal organic framework (MOF-199) for electrocatalytic water oxidation. RSC Adv 6(81):77358–77365

    Article  CAS  Google Scholar 

  42. Alizadeh N, Salimi A, Sham T-K, Bazylewski P, Fanchini G (2020) Intrinsic enzyme-like activities of cerium oxide nanocomposite and its application for extracellular H2O2 detection using an electrochemical microfluidic device. ACS Omega 5:11883–11894

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  43. Alizadeh N, Ghasemi S, Salimi A, Sham T-K, Hallaj R (2020) CuO nanorods as a laccase mimicking enzyme for highly sensitive colorimetric and electrochemical dual biosensor: application in living cell epinephrine analysis. Colloids Surf B: Biointerfaces 111228

  44. Guan H-Y, LeBlanc RJ, Xie S-Y, Yue Y (2018) Recent progress in the syntheses of mesoporous metal–organic framework materials. Coord Chem Rev 369:76–90

    Article  CAS  Google Scholar 

  45. Jiang H, Zhou J, Wang C, Li Y, Chen Y, Zhang M (2017) Effect of cosolvent and temperature on the structures and properties of Cu-MOF-74 in low-temperature NH3-SCR. Ind Eng Chem Res 56(13):3542–3550

    Article  CAS  Google Scholar 

  46. Wzgarda-Raj K, Rybarczyk-Pirek A, Wojtulewski S, Pindelska E, Palusiak M (2019) Oxidation of 2-mercaptopyridine N-oxide upon iodine agent: structural and FT-IR studies on charge-assisted hydrogen bonds CAHB (+) and I… I halogen interactions in 2, 2′-dithiobis (pyridine N-oxide) ionic cocrystal. Struct Chem 30(3):827–833

    Article  CAS  Google Scholar 

  47. Tian P, Liu D, Li K, Yang T, Wang J, Liu Y, Zhang S (2017) Porous metal-organic framework Cu3(BTC)2 as catalyst used in air-cathode for high performance of microbial fuel cell. Bioresour Technol 244:206–212

  48. Gao P, Sun X-Y, Liu B, Lian H-T, Liu X-Q, Shen J-S (2018) Cu MOF-based catalytic sensing for formaldehyde. J Mater Chem C 6(30):8105–8114

    Article  CAS  Google Scholar 

  49. Yan Y, Yao P, Mu Q, Wang L, Mu J, Li X, Kang S-Z (2011) Electrochemical behavior of amino-modified multi-walled carbon nanotubes coordinated with cobalt porphyrin for the oxidation of nitric oxide. Appl Surf Sci 258(1):58–63

    Article  CAS  Google Scholar 

  50. Brown MD, Schoenfisch MH (2018) Catalytic selectivity of metallophthalocyanines for electrochemical nitric oxide sensing. Electrochim Acta 273:98–104

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  51. Yusoff N, Rameshkumar P, Shahid MM, Huang S-T, Huang NM (2017) Amperometric detection of nitric oxide using a glassy carbon electrode modified with gold nanoparticles incorporated into a nanohybrid composed of reduced graphene oxide and Nafion. Microchim Acta 184(9):3291–3299

    Article  CAS  Google Scholar 

  52. Xu H, Liao C, Liu Y, Ye B-C, Liu B (2018) Iron phthalocyanine decorated nitrogen-doped graphene biosensing platform for real-time detection of nitric oxide released from living cells. Anal Chem 90(7):4438–4444

    Article  CAS  PubMed  Google Scholar 

  53. Ting SL, Guo CX, Leong KC, Kim D-H, Li CM, Chen P (2013) Gold nanoparticles decorated reduced graphene oxide for detecting the presence and cellular release of nitric oxide. Electrochim Acta 111:441–446

    Article  CAS  Google Scholar 

  54. M.Y. Kim, M.H. Naveen, N.G. Gurudatt, Y.B. Shim, Detection of nitric oxide from living cells using polymeric zinc organic framework-derived zinc oxide composite with conducting polymer, small 13(26) (2017) 1700502

  55. Bhat SA, Pandit SA, Rather MA, Rather GM, Rashid N, Ingole PP, Bhat MA (2017) Self-assembled AuNPs on Sulphur-doped graphene: a dual and highly efficient electrochemical sensor for nitrite (NO2−) and nitric oxide (NO). New J Chem 41(16):8347–8358

  56. Ng SR, Guo CX, Li CM (2011) Highly sensitive nitric oxide sensing using three-dimensional graphene/ionic liquid nanocomposite. Electroanalysis 23(2):442–448

    Article  CAS  Google Scholar 

  57. Dang X, Hu C, Wang Y, Hu S (2011) Gold nanoparticle film grown on quartz fiber and its application as a microsensor of nitric oxide. Sensors Actuators B Chem 160(1):260–265

    Article  CAS  Google Scholar 

  58. Liu Z, Nemec-Bakk A, Khaper N, Chen A (2017) Sensitive electrochemical detection of nitric oxide release from cardiac and cancer cells via a hierarchical nanoporous gold microelectrode. Anal Chem 89(15):8036–8043

    Article  CAS  PubMed  Google Scholar 

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Acknowledgements

The authors acknowledge the financial support from the Research Office of University of Kurdistan (grant number 4.1404086) and Iranian Nanotechnology Initiative Funds for research on microfluidic-based sensors. We thank Dr. Aso Navaee for analysis and fitting of XPS data and participation in discussions.

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Authors and Affiliations

  1. Department of Chemistry, University of Kurdistan, Sanandaj, 66177-15175, Iran

    Negar Alizadeh & Abdollah Salimi

  2. Research Center for Nanotechnology, University of Kurdistan, Sanandaj, 66177-15175, Iran

    Abdollah Salimi

  3. University of Western Ontario, London, Ontario, N6A 5B7, Canada

    Tsun-Kong Sham

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  1. Negar Alizadeh
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  2. Abdollah Salimi
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Correspondence to Abdollah Salimi.

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Alizadeh, N., Salimi, A. & Sham, TK. CuO/Cu-MOF nanocomposite for highly sensitive detection of nitric oxide released from living cells using an electrochemical microfluidic device. Microchim Acta 188, 240 (2021). https://doi.org/10.1007/s00604-021-04891-1

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