Analytical and Bioanalytical Chemistry

, Volume 411, Issue 12, pp 2545–2553 | Cite as

A water-soluble fluorescent probe for detecting creatinine in totally aqueous media and imaging exogenous creatinine in living cells

  • Fangkai Du
  • Mengru Li
  • Yanye Wei
  • Donglian Huang
  • Yan Zhou
  • Lifang YangEmail author
  • Jian Chen
  • Shaogang Liu
  • Xuecai TanEmail author
Research Paper


The design of vigorous tools for creatinine determination is extremely important in the diagnosis and treatment of kidney diseases. In the study, we examine a robust fluorescent turn-on probe (NCP-Pd) for creatinine detection in a completely aqueous solution based on the metal palladium-catalyzed reaction. In the presence of creatinine, the NCP-Pd dissociates and subsequently restores the fluorescence due to elimination of the heavy atom quenching effect and prevention of the photoinduced electron transfer effect. The probe NCP-Pd displays excellent detecting performance with respect to creatinine such as good water solubility, high selectivity, and a low detection limit (0.16 μM). Additionally, in order to ensure its clinical application, this probe is operated in blood serum samples for detecting creatinine and compared with a commercial clinical method. The results indicate an extremely high agreement with the commercial clinical method. Furthermore, the results confirm that the probe NCP-Pd exhibits satisfactory cell permeability and low cytotoxicity and can detect creatinine in L929 and HCT116 cells. The study provides a potential application for detecting creatinine and conducting pathological research on creatinine-involved diseases.


Fluorescent probe Creatinine Blood Living cells Imaging 


Funding information

This work was supported by the National Sciences Foundation of China (21503043, 21365004, 81560713), the Natural Science Foundation of Guangxi (2018GXNSFAA294044, 2018GXNSFAA281136, 2017GXNSFBA198026, 2015jjCA20003), Specific Research Project of Guangxi for Research Bases and Talents (AD18126005), the Scientific Research Fund of Guangxi Education Department (2013ZD019), the Basic Ability Enhancement Program for Young and Middle-aged Teachers of Guangxi (2018KY0168), and the Xiangsihu Young Scholars Innovative Research Team of Guangxi University for Nationalities and Innovation Project of Guangxi Graduate Education (gxun-chxzs2018060).

Compliance with ethical standards

Patient sera were collected in accordance with the code of conduct of research with human material in China. This study was approved by the Ethics Committee at the hospital of Guangxi University for Nationalities. Informed consent was obtained from all participants included in the study.

Conflict of interest

The authors declare that they have no conflict of interest.

Supplementary material

216_2019_1695_MOESM1_ESM.pdf (795 kb)
ESM 1 (PDF 795 kb)


  1. 1.
    Killard AJ, Smyth MR. Creatinine biosensors: principles and designs. Trends Biotechnol. 2000;18:433–7.CrossRefGoogle Scholar
  2. 2.
    Narayanau S, Appleton HD. Creatinine: a review. Clin Chem. 1980;26:1119–26.Google Scholar
  3. 3.
    Schiffl H, Lang SM. Update on biomarkers of acute kidney injury. Mol Diagn Ther. 2012;16:199–207.CrossRefGoogle Scholar
  4. 4.
    Gamagedara S, Shi H, Ma Y. Quantitative determination of taurine and related biomarkers in urine by liquid chromatography-tandem mass spectrometry. Anal Bioanal Chem. 2012;402:763–70.CrossRefGoogle Scholar
  5. 5.
    Spencer K. Analytical reviews in clinical biochemistry: the estimation of creatinine. Ann Clin Biochem. 1986;23:1–25.CrossRefGoogle Scholar
  6. 6.
    An SS, Nanda SS, Yi DK. Measurement of creatinine in human plasma using a functional porous polymer structure sensing motif. Int J Nanomedicine. 2015;10:93–9.CrossRefGoogle Scholar
  7. 7.
    Udy A, O’Donoghue S, D’Intini V, Healy H, Lipman J. Point of care measurement of plasma creatinine in critically ill patients with acute kidney injury. Anaesthesia. 2009;64:403–7.CrossRefGoogle Scholar
  8. 8.
    Randviir EP, Banks CE. Analytical methods for quantifying creatinine within biological media. Sensors Actuators B Chem. 2013;183:239–52.CrossRefGoogle Scholar
  9. 9.
    Delanghe JR, Speeckaert MM. Creatinine determination according to Jaffe-what does it stand for? Ndt Plus. 2011;4:83–6.Google Scholar
  10. 10.
    Weber JA, van Zanten AP. Interferences in current methods for measurements of creatinine. Clin Chem. 1991;37:695–700.Google Scholar
  11. 11.
    Nguyen VK, Wolff CM, Seris JL, Schwing JP. Immobilize enzyme electrode for creatinine determination in serum. Anal Chem. 1991;63:611–4.CrossRefGoogle Scholar
  12. 12.
    Jiang Y, Cheng X, Wang C, Ma Y. Quantitative determination of sarcosine and related compounds in urinary samples by liquid chromatography with tandem mass spectrometry. Anal Chem. 2010;82:9022–7.CrossRefGoogle Scholar
  13. 13.
    Stosch R, Henrion A, Schiel D, Güttler B. Surface-enhanced Raman scattering based approach for quantitative determination of creatinine in human serum. Anal Chem. 2005;77:7386–92.CrossRefGoogle Scholar
  14. 14.
    Yadav S, Devi R, Kumar A, Pundir CS. Tri-enzyme functionalized ZnO-NPs/CHIT/c-MWCNT/PANI composite film for amperometric determination of creatinine. Biosens Bioelectron. 2011;28:64–70.CrossRefGoogle Scholar
  15. 15.
    Júnior IM, Pasquini C. Automated monosegmented flow analyser. Determination of glucose, creatinine and urea. Analyst. 1997;122:1039–44.CrossRefGoogle Scholar
  16. 16.
    Chen X, Wang F, Hyun JY, Wei T, Qiang J, Ren X, et al. Recent progress in the development of fluorescent, luminescent and colorimetric probes for detection of reactive oxygen and nitrogen species. Chem Soc Rev. 2016;45:2976–3016.CrossRefGoogle Scholar
  17. 17.
    Chen J, Li Y, Lv K, Zhong W, Wang H, Wu Z, et al. Cyclam-functionalized carbon dots sensor for sensitive and selective detection of copper(II) ion and sulfide anion in aqueous media and its imaging in live cells. Sensors Actuators B Chem. 2016;224:298–306.CrossRefGoogle Scholar
  18. 18.
    Yu CM, Li XZ, Zeng F, Zheng FY, Wu SZ. Carbon-dot-based ratiometric fluorescent sensor for detecting hydrogen sulfide in aqueous media and inside live cells. Chem Commun. 2013;49:403–5.CrossRefGoogle Scholar
  19. 19.
    Zeng RJ, Gao Q, Cheng FM, Yang YS, Zhang PS, Chen S, et al. A near-infrared fluorescent sensor with large Stokes shift for rapid and highly selective detection of thiophenols in water samples and living cells. Anal Bioanal Chem. 2018;410:2001–9.CrossRefGoogle Scholar
  20. 20.
    Wu Y, Wang J, Zeng F, Huang S, Huang J, Xie H, et al. Pyrene derivative emitting red or near-infrared light with monomer/excimer conversion and its application to ratiometric detection of hypochlorite. ACS Appl Mater Interfaces. 2016;8:1511–9.CrossRefGoogle Scholar
  21. 21.
    Huang Y, Zhang P, Gao M, Zeng F, Qin A, Wu S, et al. Ratiometric detection and imaging of endogenous hypochlorite in live cells and in vivo achieved by using an aggregation induced emission (AIE)-based nanoprobe. Chem Commun. 2016;52:7288–91.CrossRefGoogle Scholar
  22. 22.
    Lee HJ, Cho MJ, Chang SK. Ratiometric signaling of hypochlorite by the oxidative cleavage of sulfonhydrazide-based rhodamine-dansyl dyad. Inorg Chem. 2015;54:8644–9.CrossRefGoogle Scholar
  23. 23.
    Wang H, Zhang P, Chen J, Li Y, Yu M, Long Y, et al. Polymer nanoparticle-based ratiometric fluorescent probe for imaging Hg2+ ions in living cells. Sensors Actuators B Chem. 2017;242:818–24.CrossRefGoogle Scholar
  24. 24.
    Chen J, Zhong W, Tang Y, Wu Z, Li Y, Yi P, et al. Amphiphilic BODIPY-based Photoswitchable fluorescent polymeric nanoparticles for rewritable patterning and dual-color cell imaging. Macromolecules. 2015;48:3500–8.CrossRefGoogle Scholar
  25. 25.
    Quadahi K, Sbargoud K, Allard E, Larpent C. FRET-mediated pH-responsive dual fluorescent nanoparticles prepared via click chemistry. Nanoscale. 2012;4:727–32.CrossRefGoogle Scholar
  26. 26.
    Tajarrod N, Rofouei MK, Masteri-Farahani M, Zadmard R. A quantum dot-based fluorescence sensor for sensitive and enzymeless detection of creatinine. Anal Methods. 2016;8:5911–20.CrossRefGoogle Scholar
  27. 27.
    Mathew MS, Joseph K. Green synthesis of gluten-stabilized fluorescent gold quantum clusters: application as turn-on sensing of human blood creatinine. ACS Sustain Chem Eng. 2017;5:4837–45.CrossRefGoogle Scholar
  28. 28.
    Pal S, Lohar S, Mukherjee M, Chattopadhyay P, Dhara K. A fluorescent probe for the selective detection of creatinine in aqueous buffer applicable to human blood serum. Chem Commun. 2016;52:13706–9.CrossRefGoogle Scholar
  29. 29.
    Ellairaja S, Shenbagavalli K, Vasantha VS. Ultrasensitive fluorescent biosensor for creatinine determination in human biofluids based on water soluble rhodamine B dye-Au3+ ions conjugate. Chemistry Select. 2017;23:1025–31.Google Scholar
  30. 30.
    Sundaram E, Subramanian V, Velayutham K, Gomathinayagam R, Vasantha VS. Michael addition based chemodosimeter for serum creatinine detection using (E)-3-(pyren-2-yl)-1-(3,4,5-trimethoxyphenyl)prop-2-en-1-one chalcone. ACS Sens. 2018;3:763–71.CrossRefGoogle Scholar
  31. 31.
    Zhang P, Wang H, Zhang D, Zeng X, Zeng R, Xiao L, et al. Two-photon fluorescent probe for lysosome-targetable hypochlorous acid detection within living cells. Sensors Actuators B Chem. 2018;255:2223–31.CrossRefGoogle Scholar
  32. 32.
    Liu HY, Chen LF, Wang HY, Wan Y, Wu H. Synthesis and photophysical properties of novel fluorescent materials containing 2,4,6-triphenylpyridine and 1,8-naphthalimide units using Suzuki reaction. RSC Adv. 2016;6:94833–9.CrossRefGoogle Scholar
  33. 33.
    La Y, Hong J, Jeong Y, Lee J. A 1,8-naphthalimide-based chemosensor fordual-mode sensing: colorimetric and fluorometric detection of multiple analytes. RSC Adv. 2016;6:84098–105.CrossRefGoogle Scholar
  34. 34.
    Guo X, Qian X, Jia L. A highly selective and sensitive fluorescent chemosensor for Hg2+ in neutral buffer aqueous solution. J Am Chem Soc. 2004;126:2272–3.CrossRefGoogle Scholar
  35. 35.
    Li Y, Wang X, Yang J, Xie X, Li M, Niu J, et al. Fluorescent probe based on azobenzene-cyclopalladium for the selective imaging of endogenous carbon monoxide under hypoxia conditions. Anal Chem. 2016;88:11154–9.CrossRefGoogle Scholar
  36. 36.
    Martin-Gil FJ, Martin-Gil J. Platinum(II) and palladium(II) complexes of creatinine. Platinum blues. Inorg Chim Acta. 1987;137:131–4.CrossRefGoogle Scholar
  37. 37.
    Panchompoo J, Aldous L, Compton RG. Irreversible uptake of palladium from aqueous systems using L-cysteine methyl ester physisorbed on carbon black. J Mater Chem. 2011;21:9513–22.CrossRefGoogle Scholar
  38. 38.
    Qu XM, Wang SP, Ge ZL, Wang JB, Yao GB, Li J, et al. Programming cell adhesion for on-chip sequential Boolean logic functions. J Am Chem Soc. 2017;139:10176–9.CrossRefGoogle Scholar
  39. 39.
    Chen LZ, Chao J, Qu XM, Zhang HB, Zhu D, Su S, et al. Probing cellular molecules with polyA-based engineered aptamer nanobeacon. ACS Appl Mater Interfaces. 2017;9:8014–20.CrossRefGoogle Scholar
  40. 40.
    Fan CH, Pei H. Special Issue of “DNA Nanotechnology”. Chin J Chem. 2016;34:251.CrossRefGoogle Scholar
  41. 41.
    Pei H, Liang L, Yao GB, Li J, Huang Q, Fan CH. Reconfigurable three-dimensional DNA nanostructures for the construction of intracellular logic sensors. Angew Chem Int Ed. 2012;51:9020–4.CrossRefGoogle Scholar

Copyright information

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

Authors and Affiliations

  • Fangkai Du
    • 1
  • Mengru Li
    • 1
  • Yanye Wei
    • 1
  • Donglian Huang
    • 1
  • Yan Zhou
    • 1
  • Lifang Yang
    • 1
    Email author
  • Jian Chen
    • 2
  • Shaogang Liu
    • 1
  • Xuecai Tan
    • 1
    Email author
  1. 1.Guangxi Key Laboratory of Chemistry and Engineering of Forest Products, Key Laboratory of Guangxi Colleges and Universities for Food Safety and Pharmaceutical Analytical ChemistrySchool of Chemistry and Chemical Engineering, Guangxi University for NationalitiesNanningChina
  2. 2.Key Laboratory of Theoretical Organic Chemistry and Functional Molecule of Ministry of Education, Hunan Provincial Key Laboratory of Controllable Preparation and Functional Application of Fine Polymers, Hunan Province College Key Laboratory of QSAR/QSPR, Institute of Functional Materials, School of Chemistry and Chemical EngineeringHunan University of Science and TechnologyXiangtanChina

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