Skip to main content
SpringerLink
Log in

Fluorescent gold nanoclusters as pH sensors for the pH 5 to 9 range and for imaging of blood cell pH values

  • Original Paper
  • Published:
Microchimica Acta Aims and scope Submit manuscript

Abstract

The authors describe the use of gold nanoclusters (AuNCs) with a diameter of ~2 nm for fluorescent sensing of pH values in the range from 5 to 9. The AuNCs were synthesized in the presence of bovine serum albumin (BSA) which acts as both a reducing agent and capping agent. The resulting AuNCs were characterized in terms of size and surface chemistry using TEM and FTIR. The BSA-capped AuNCs display red luminescence, with excitation/emission peaks at 470/640 nm, which is strongly modulated by the pH indicator bromothymol blue (BTB). The effect depends mainly on an inner filter effect due to spectral overlap between the absorption BTB and the emission of the AuNCs. The pH nanosensor responds to pH values in the range from 5 to 9 which is the so-called physiological pH range. The method was applied to detect changes in the pH values that occur after the death of red blood cells. Such pH changes are considered as a potential forensic marker for estimating the time passed since death. The results show the BTB-BSA-AuNC system to be capable of detecting respective intracellular pH changes.

Schematic presentation of gold nanoclusters capped with bovine serum albumin whose red luminescence is modulated by the pH indicator bromothymol blue. The nanoclusters were applied as pH sensor in solution (5–9) and in blood cell imaging to estimate the time passed since death.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5
Fig. 6
Fig. 7

Similar content being viewed by others

References

  1. Busa WB, Nuccitelli R (1984) Metabolic regulation via intracellular pH. Am J Physiol Regul Integr Comp Physiol 246:R409–R438

    CAS  Google Scholar 

  2. Putney LK, Barber DL (2003) Na-H exchange-dependent increase in intracellular pH times G2/M entry and transition. J Biol Chem 278:44645–44469

    Article  CAS  Google Scholar 

  3. Madshus IH (1988) Regulation of intracellular pH in eukaryotic cells. Biochem J 250:1–8

    Article  CAS  Google Scholar 

  4. Walenta S, Wetterling M, Lehrke M, Schwickert G, Sundfør K, Rofstad EK, Mueller-Klieser W (2000) High lactate levels predict likelihood of metastases, tumor recurrence, and restricted patient survival in human cervical cancers. Cancer res 60:916–921

    CAS  Google Scholar 

  5. Damaghi M, Wojtkowiak JW, Gillies RJ (2013) pH sensing and regulation in cancer. Front Physiol 4:370

    Article  Google Scholar 

  6. Donaldson AE, Lamont IL (2013) Biochemistry changes that occur after death: potential markers for determining post-mortem interval. PLoS One 8:e82011

    Article  Google Scholar 

  7. Hesse SJ, Ruijter GJ, Dijkema C, Visser J (2000) Measurement of intracellular (compartmental) pH by 31P NMR in Aspergillus niger. J Biotechnol 77:5–15

    Article  CAS  Google Scholar 

  8. Orgovan G, Noszal B (2011) Electrodeless, accurate pH determination in highly basic media using a new set of (1)H NMR pH indicators. J Pharm Biomed Anal 54:958–964

    Article  CAS  Google Scholar 

  9. Li Y, Wang Y, Yang S, Zhao Y, Yuan L, Zheng J, Yang R (2015) Hemicyanine-based high resolution ratiometric near-infrared fluorescent probe for monitoring pH changes in vivo. Anal Chem 87:2495–2503

    Article  CAS  Google Scholar 

  10. Zhou X, Su F, Lu H, Senechal-Willis P, Tian Y, Johnson RH, Meldrum DR (2012) An FRET-based ratiometric chemosensor for in vitro cellular fluorescence analyses of pH. Biomaterials 33:171–180

    Article  CAS  Google Scholar 

  11. Bizzarri R, Serresi M, Luin S, Beltram F (2009) Green fluorescent protein based pH indicators for in vivo use: a review. Anal Bioanal Chem 393:1107–1122

    Article  CAS  Google Scholar 

  12. Keith BM, Bernard L, Sabahudin H, Geoff S, John HT (2008) Assessment of cytotoxicity of quantum dots andGold nanoparticles using cell-based ImpedanceSpectroscopy. Anal Chem 80:5487–5493

    Article  Google Scholar 

  13. Knopp D, Tang D, Niessner R (2009) Review: bioanalytical applications of biomolecule-functionalized nanometer-sized doped silica particles. Anal Chim Acta 647:14–30

    Article  CAS  Google Scholar 

  14. Sun LN, Peng H, Stich MI, Achatz D, Wolfbeis OS (2009) pH sensor based on upconverting luminescent lanthanide nanorods. Chem Commun (Camb) 33:5000–5002

    Article  Google Scholar 

  15. Chen LY, Wang CW, Yuan Z, Chang HT (2015) Fluorescent gold nanoclusters: recent advances in sensing and imaging. Anal Chem 87:216–229

    Article  CAS  Google Scholar 

  16. Khandelia R, Bhandari S, Pan UN, Ghosh SS, Chattopadhyay A (2015) Gold Nanocluster embedded albumin nanoparticles for two-photon imaging of cancer cells accompanying drug delivery. Small 11:4075–4081

    Article  CAS  Google Scholar 

  17. Lee D, Donkers RL, Wang G, Harper AS, Murray RW (2004) Electrochemistry and optical absorbance and luminescence of molecule-like Au38 nanoparticles. J am Chem Soc 126:6193–6199

    Article  CAS  Google Scholar 

  18. Negishi Y, Nobusada K, Tsukuda T (2005) Glutathione-protected gold clusters revisited: bridging the gap between gold(I)-thiolate complexes and thiolate-protected gold nanocrystals. J am Chem Soc 127:5261–5270

    Article  CAS  Google Scholar 

  19. Xu Y, Sherwood J, Qin Y, Crowley D, Bonizzoni M, Bao Y (2014) The role of protein characteristics in the formation and fluorescence of au nanoclusters. Nano 6:1515–1524

    CAS  Google Scholar 

  20. Wang M, Mei Q, Zhang K, Zhang Z (2012) Protein-gold nanoclusters for identification of amino acids by metal ions modulated ratiometric fluorescence. Analyst 137:1618–1623

    Article  CAS  Google Scholar 

  21. Lin CAJ, Yang TY, Lee CH, Huang SH, Sperling RA, Zanella M, Li JK, Shen JL, Wang HH, Yeh HI, Parak, WJ, Chang WH (2009) Synthesis, characterization, and bioconjugation of fluorescent gold nanoclusters toward biological labeling applications. ACS Nano 3:395–401

  22. Xie J, Zheng Y, Ying JY (2010) Highly selective and ultrasensitive detection of hg(2+) based on fluorescence quenching of au nanoclusters by hg(2+) -au(+) interactions. Chem Commun (Camb) 46:961–963

    Article  CAS  Google Scholar 

  23. Xie J, Zheng Y, Ying JY (2009) Protein-directed synthesis of highly fluorescent gold nanoclusters. J am Chem Soc 131:888–889

    Article  CAS  Google Scholar 

  24. Ding C, Tian Y (2014) Gold nanocluster-based fluorescence biosensor for targeted imaging in cancer cells and ratiometric determination of intracellular pH. Biosens Bioelectron 65C:183–190

    Google Scholar 

  25. Deng HH, Wu GW, Zou ZQ, Peng HP, Liu AL, Lin XH, Xia XH, Chen W (2015) pH-sensitive gold nanoclusters: preparation and analytical applications for urea, urease, and urease inhibitor detection. Chem Commun (Camb) 51:7847–7850

    Article  CAS  Google Scholar 

  26. Ali R, Saleh SM, Meier RJ, Azab HA, Abdelgawad I, Wolfbeis OS (2010) Upconverting nanoparticle based optical sensor for carbon dioxide. Sens Actuators B Chem 150:126–131

    Article  CAS  Google Scholar 

  27. Vidal E, Palomeque ME, Lista AG, Fernandez Band BS (2003) Flow injection analysis: Rayleigh light scattering technique for total protein determination. Anal Bioanal Chem 376:38–41

    Article  CAS  Google Scholar 

  28. Zhou XC, Yan CQ, Yan CN (2010) Study on the interaction of bromothymol blue and bovine serum albumin[J]. Chemical Research and Application 1:003

    Google Scholar 

  29. Lin CA, Lee CH, Hsieh JT, Wang HH, Li JK, Shen JL, Chan WH, Yeh HI, Chang WH (2009) Review: synthesis of fluorescent metallic nanoclusters toward biomedical application: recent progress and present challenges. J med Biol Eng 29:276–283

    CAS  Google Scholar 

  30. Chakraborty D, Rajan G, Isaac R (2015) A splendid blend of nanotechnology and forensic Science. Journal of Nanotechnology in Engineering and Medicine 6:010801–010806

    Article  Google Scholar 

  31. Chang HC, Ho JA (2015) Gold Nanocluster-assisted fluorescent detection for hydrogen peroxide and cholesterol based on the inner filter effect of gold nanoparticles. Anal Chem 87:10362–10367

    Article  CAS  Google Scholar 

  32. Baumann D, Hofmann D, Nullmeier S, Panther P, Dietze C, Musyanovych A, Ritz S, Landfester K, Mailänder V (2013) Complex encounters: nanoparticles in whole blood and their uptake into different types of white blood cells. Nanomedicine 8:699–713

    Article  CAS  Google Scholar 

  33. Hsu NY, Lin YW (2016) Microwave-assisted synthesis of bovine serum albumin–gold nanoclusters and their fluorescence-quenched sensing of Hg2+ ions. New J Chem 40:1155–1161

    Article  CAS  Google Scholar 

  34. Wang XL, Jie YA, Kui JI (2008) Electrochemical study on the interaction of protein with Bromothymol blue and its analytical application. Chem Res Chin Univ 24:701–706

    Google Scholar 

  35. Silverstein RM, Webster FX, Kiemle DJ (2005) Spectrometric identification of organic compounds. Wiley, New Delhi, pp 107–108

    Google Scholar 

  36. Donaldson AE, Lamont IL (2014) Estimation of post-mortem interval using biochemical markers. Aust J Forensic Sci 46:8–26

    Article  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Chemistry Department, Faculty of Science, Suez University, Suez, 43518, Egypt

    Reham Ali

  2. Chemistry Branch, Department of Science and Mathematics, Faculty of Petroleum and Mining Engineering, Suez University, Suez, 43721, Egypt

    Sayed M. Saleh

  3. Department of Forensic Medicine & Clinical Toxicology, Faculty of Medicine, Suez Canal University, Ismailia, 41522, Egypt

    Sanaa M. Aly

Authors
  1. Reham Ali
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Sayed M. Saleh
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Sanaa M. Aly
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Reham Ali.

Ethics declarations

The author(s) declare that they have no competing interests.

Electronic supplementary material

ESM 1

(DOCX 341 kb)

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Ali, R., Saleh, S.M. & Aly, S.M. Fluorescent gold nanoclusters as pH sensors for the pH 5 to 9 range and for imaging of blood cell pH values. Microchim Acta 184, 3309–3315 (2017). https://doi.org/10.1007/s00604-017-2352-7

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00604-017-2352-7

Keywords

Search

Navigation