Skip to main content
SpringerLink
Log in

An integrated lab-on-a-chip-based electrochemical biosensor for rapid and sensitive detection of cancer biomarkers

  • Research Paper
  • Published:
Analytical and Bioanalytical Chemistry Aims and scope Submit manuscript

Abstract

Recent advances in the area of biosensor technology and microfluidic applications have enabled the miniaturisation of the sensing platforms. Here we describe a new integrated and fully automated lab-on-a-chip-based biosensor device prototype (MiSens) that has potential to be used for point-of-care cancer biomarker testing. The key features of the device include a new biochip, a device integrated microfluidic system and real-time amperometric measurements during the flow of enzyme substrate. For ease of use, a new plug and play type sensor chip docking station has been designed. This system allows the formation of an ∼7 μL capacity flow cell on the electrode array with the necessary microfluidic and electronic connections with one move of a handle. As a case study, the developed prototype has been utilised for the detection of prostate-specific antigen (PSA) level in serum that is routinely used as a biomarker for the diagnosis of prostate cancer. The patient samples from a nearby hospital have been collected and tested using the MiSens device, and the results have been compared to the hospital results. The obtained results indicate the potential of the MiSens device as a useful tool for point-of-care testing.

Microfluidics integrated and automated electrochemical biosensor device “MiSens” has been designed and fabricated by a multidisciplinary team and utilised to detect PSA from clinical samples.

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

Similar content being viewed by others

References

  1. Frost&Sullivan. Analytical review of world biosensors market N810-32 2010.

  2. The Lewin Group I. The value of diagnostics innovation, adoption and diffusion into health care. http://www.socalbio.org/pdfs/thevalueofdiagnostics.pdf 2005.

  3. Healy DA, Hayes CJ, Leonard P, et al. Biosensor developments: application to prostate-specific antigen detection. Trends Biotech. 2007;25(3):125–31.

    Article  CAS  Google Scholar 

  4. Wu J, Fu Z, Yan F, Ju H. Biomedical and clinical applications of immunoassays and immunosensors for tumor markers. Trac-Trend Anal Chem. 2007;26(7):679–88.

    Article  CAS  Google Scholar 

  5. Tothill IE. Biosensors for cancer markers diagnosis. Semin Cell Dev Biol. 2009;20(1):55–62.

    Article  CAS  Google Scholar 

  6. Eicher D, Merten CA. Microfluidic devices for diagnostic applications. Expert Rev Mol Diagn. 2011;11(5):505–19.

    Article  Google Scholar 

  7. Gervais L, de Rooij N, Delamarche E. Microfluidic chips for point-of-care immunodiagnostics. Adv Mater. 2011;23(24):H151–76.

    Article  CAS  Google Scholar 

  8. Trietsch SJ, Hankemeier T, van der Linden HJ. Lab-on-a-chip technologies for massive parallel data generation in the life sciences: a review. Chemometr Intell Lab. 2011;108(1):64–75.

    Article  CAS  Google Scholar 

  9. Temiz Y, Lovchik RD, Kaigala GV, Delamarche E. Lab-on-a-chip devices: how to close and plug the lab? Microelectron Eng. 2015;132:156–75.

    Article  CAS  Google Scholar 

  10. Dulay SB, Gransee R, Julich S, et al. Automated microfluidically controlled electrochemical biosensor for the rapid and highly sensitive detection of Francisella tularensis. Biosens Bioelectron. 2014;59:342–9.

    Article  CAS  Google Scholar 

  11. Shah J, Wilkins E. Electrochemical biosensors for detection of biological warfare agents. Electroanal. 2003;15(3):157–67.

    Article  CAS  Google Scholar 

  12. Mulchandani A, Rogers KR. Enzyme and microbial biosensors, techniques and protocols. Totowa: Humana Press; 1998.

    Book  Google Scholar 

  13. Chikkaveeraiah BV, Mani V, Patel V, et al. Microfluidic electrochemical immunoarray for ultrasensitive detection of two cancer biomarker proteins in serum. Biosens Bioelectron. 2011;26(11):4477–83.

    Article  CAS  Google Scholar 

  14. Mascini M, Tombelli S. Biosensors for biomarkers in medical diagnostics. Biomarkers. 2008;13(7–8):637–57.

    Article  CAS  Google Scholar 

  15. Ferlay J, Autier P, Boniol M, et al. Estimates of the cancer incidence and mortality in Europe in 2006. Ann Oncol. 2007;18(3):581–92.

    Article  CAS  Google Scholar 

  16. Diamandis EP. Prostate-specific antigen: its usefulness in clinical medicine. Trends Endocrin Met. 1998;9(8):310–6.

    Article  CAS  Google Scholar 

  17. Brawer MK, Lange PH. PSA in the screening, staging and follow-up of early-stage prostate cancer. A review of recent developments. World J Urol. 1989;7(1):7–11.

    Article  Google Scholar 

  18. Uludag Y, Sagiroglu M, Ersoy A et al. An electrochemical sensor array and apparatus, PCT/IB2015/052479. In, 2015.

  19. Uludag Y, Hammond R, Cooper MA. A signal amplification assay for HSV type 1 viral DNA detection using nanoparticles and direct acoustic profiling. J Nanobio. 2010;8:3.

    Article  Google Scholar 

  20. Uludag Y, Tothill IE. Development of a sensitive detection method of cancer biomarkers in human serum (75%) using a quartz crystal microbalance sensor and nanoparticles amplification system. Talanta. 2010;82(1):277–82.

    Article  CAS  Google Scholar 

  21. Uludag Y, Tothill IE. Cancer biomarker detection in serum samples using surface plasmon resonance and quartz crystal microbalance sensors with nanoparticle signal amplification. Anal Chem. 2012;84(14):5898–904.

    Article  CAS  Google Scholar 

  22. Olcer Z, Esen E, Muhammad T, et al. Fast and sensitive detection of mycotoxins in wheat using microfluidics based real-time electrochemical profiling. Biosens Bioelectron. 2014;62:163–9.

    Article  CAS  Google Scholar 

  23. Uludag Y, Olcer Z, Samil SM. Design and characterisation of a thin-film electrode array with shared reference/counter electrodes for electrochemical detection. Biosens Bioelectron. 2014;57:85–90.

    Article  CAS  Google Scholar 

  24. Yang Z, Zhang Y, Itoh T, Maeda R. A novel MEMS compatible lab-on-a-tube technology. Lab Chip. 2014;14(24):4604–8.

    Article  CAS  Google Scholar 

  25. Huang Y, Mason AJ. Lab-on-CMOS integration of microfluidics and electrochemical sensors. Lab Chip. 2013;13(19):3929–34.

    Article  CAS  Google Scholar 

  26. Uludag Y, Sagiroglu M, Ersoy A et al. Electrochemical sensor array and its casette. In: TP Office, ed. PT 2014/3992. Turkey, 2014.

  27. Campuzano S, Pedrero M, Montemayor C, et al. Characterization of alkanethiol-self-assembled monolayers-modified gold electrodes by electrochemical impedance spectroscopy. J Electroanal. 2006;586(1):112–21.

    Article  CAS  Google Scholar 

  28. Yang YJ, Khoo SB. Fabrication of self-assembled monolayer of 8-mercaptoquinoline on polycrystalline gold electrode and its selective catalysis for the reduction of metal ions and the oxidation of biomolecules. Sensors Actuat B-Chem. 2004;97(2–3):221–30.

    Article  CAS  Google Scholar 

  29. Soukka T, Antonen K, Harma H, et al. Highly sensitive immunoassay of free prostate-specific antigen in serum using europium(III) nanoparticle label technology. Clini Chim Acta. 2003;328(1–2):45–58.

    Article  CAS  Google Scholar 

  30. Erturk G, Hedstrom M, Tumer MA, et al. Real-time prostate-specific antigen detection with prostate-specific antigen imprinted capacitive biosensors. Anal Chim Acta. 2015;891:120–9.

    Article  CAS  Google Scholar 

  31. Zhang B, Zhang X, Yan H, et al. A novel multi-array immunoassay device for tumor markers based on insert-plug model of piezoelectric immunosensor. Biosens Bioelectron. 2007;23(1):19–25.

    Article  Google Scholar 

  32. Ding YJ, Lu HX, Shi GR, et al. Cell-based immobilization strategy for sensitive piezoelectric immunoassay of total prostate specific antigen. Biosens Bioelectron. 2008;24(2):228–32.

    Article  CAS  Google Scholar 

  33. Yang L, Zhao H, Deng GG, et al. Immunosensor for prostate-specific antigen using Au/Pd@flower-like SnO2 as platform and Au@mesoporous carbon as signal amplification. RSC Adv. 2015;5(90):74046–53.

    Article  CAS  Google Scholar 

  34. Wang D, Zheng YN, Chai YQ, et al. Target protein induced cleavage of a specific peptide for prostate-specific antigen detection with positively charged gold nanoparticles as signal enhancer. Chem Commun. 2015;51(52):10521–3.

    Article  CAS  Google Scholar 

Download references

Acknowledgments

The project is supported by BILGEM-TUBITAK (The Scientific and Technological Research Council of Turkey) (grant no: S569000 and 100121) and the Republic of Turkey Ministry of Development Infrastructure Grant (no: 2011K120020). We gratefully acknowledge Aylin Ersoy, Atike Demiralp, Hakkı Aktepe, Tugba Yurt and Muammer Karadağ from BILGEM-TUBITAK for their contribution to the fabrication of the electrode arrays and the device. We gratefully acknowledge Dr. Hasan Güner and Dr. Erol Özgür from Bilkent University for their help with XPS measurements.

Author information

Authors and Affiliations

  1. Bioelectronic Devices and Systems Group, UEKAE-BILGEM-The Scientific and Technological Research Council of Turkey (TUBITAK), 41470, Gebze, Kocaeli, Turkey

    Yildiz Uludag, Güzin Köktürk, M. Yağmur Gök, Mete Akgün, Serkan Barut & Sinan Budak

  2. Kartal Dr .Lütfi Kırdar Education and Research Hospital Urology Clinic, 34890, Kartal, İstanbul, Turkey

    Fehmi Narter & Erkin Sağlam

Authors
  1. Yildiz Uludag
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Fehmi Narter
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Erkin Sağlam
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Güzin Köktürk
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. M. Yağmur Gök
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Mete Akgün
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Serkan Barut
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Sinan Budak
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Yildiz Uludag.

Ethics declarations

Conflict of interest

On behalf of myself and other co-authors, I state that there is no conflict of interest in this paper.

Ethical approval

Patient samples were collected from Kartal Lütfi Kırdar Education and Research Hospital (İstanbul, Turkey). The ethical approval was obtained from the same hospital’s Research Ethics Committee. All the participants gave their informed consent before sample collection.

Electronic supplementary material

Below is the link to the electronic supplementary material.

ESM 1

(PDF 1310 kb)

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Uludag, Y., Narter, F., Sağlam, E. et al. An integrated lab-on-a-chip-based electrochemical biosensor for rapid and sensitive detection of cancer biomarkers. Anal Bioanal Chem 408, 7775–7783 (2016). https://doi.org/10.1007/s00216-016-9879-z

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00216-016-9879-z

Keywords

Search

Navigation