Skip to main content
SpringerLink
Log in

Developing an integrated microfluidic and miniaturized electrochemical biosensor for point of care determination of glucose in human plasma samples

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

Abstract

A cost-effective, point of care (POC) device based on highly oriented CNT arrays was developed as an electrochemical assay for real-time and sensitive detection of glucose in complex samples. A low-cost, microcontroller-based potentiostat consisting of Arduino Due and LMP9100-EVM was developed to perform electrochemical measurements such as cyclic voltammetry (CV) and amperometry. A syringe pump based on open-source electronics was designed to direct the flow through a microfluidic chip. Vertically aligned carbon nanotube (VACNT) sensor arrays, in combination with the miniature potentiostat and the syringe pumps, were utilized as a POC device for the rapid and accurate detection of glucose. The structure and morphology of samples were characterized by field emission scanning electron microscopy (FESEM) and attenuated total reflectance Fourier transform infrared spectrometry (ATR-FTIR). CV as well as electrochemical impedance spectroscopy (EIS) was performed to investigate the electrochemical behavior of the electrode with respect to different diffusion regimes. The mediator-less biosensor had a limit of detection of 23 μM and sensitivity of 1462 μA mM−1 cm−2 and 1050 μA mM−1 cm−2 at the linear range of 1.2–7.8 mM and 7.8–11.2 mM, respectively. The presence of other biological compounds such as uric acid (UA) and ascorbic acid (AA) did not interfere with the detection of glucose. Finally, the designed POC device was successfully applied for the determination of glucose in human blood plasma samples.

Graphical abstract

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
Fig. 8

Similar content being viewed by others

References

  1. Scognamiglio V. Nanotechnology in glucose monitoring: advances and challenges in the last 10 years. Biosens Bioelectron. 2013;47:12–5.

    Article  CAS  PubMed  Google Scholar 

  2. McIntyre HD, Catalano P, Zhang C, Desoye G, Mathiesen ER, Damm P. Gestational diabetes mellitus. Nat Rev. 2019;5(1):1–19.

    Google Scholar 

  3. Vu N, Narvaez-Rivas M, Chen GY, Rewers MJ, Zhang Q. Accurate mass and retention time library of serum lipids for type 1 diabetes research. Anal Bioanal Chem. 2019;411(23):5937–49.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  4. Hussain S, Park SY. Optical glucose biosensor based on photonic interpenetrating polymer network with solid-state cholesteric liquid crystal and cationic polyelectrolyte. Sens. Actuators, B. 2020:128099.

  5. Muscatello MMW, Stunja LE, Asher SA. Polymerized crystalline colloidal array sensing of high glucose concentrations. Anal Chem. 2009;81:4978–86.

    Article  PubMed  Google Scholar 

  6. Wahab HA, Salama AA, El Saeid AA, Willander M, Nur O, Battisha IK. Zinc oxide nano-rods based glucose biosensor devices fabrication. Results Phys. 2018;9:809–14.

    Article  Google Scholar 

  7. Guadarrama-Fernández L, Novell M, Blondeau P, Andrade FJ. A disposable, simple, fast and low-cost paper-based biosensor and its application to the determination of glucose in commercial orange juices. Food Chem. 2018;265:64–9.

    Article  PubMed  Google Scholar 

  8. Benito-Peña E, Valdés MG, Glahn-Martínez B, Moreno-Bondi MC. Fluorescence based fiber optic and planar waveguide biosensors. A review Anal Chim Acta. 2016;943:17–40.

    Article  PubMed  Google Scholar 

  9. Bobrowski T, Schuhmann W. Long-term implantable glucose biosensors. Curr Opin Electrochem. 2018;10:112–9.

    Article  CAS  Google Scholar 

  10. Wang Z, Kimura M, Ono T. Manufacturing and characterization of simple cantilever thermal biosensor with Si-metal thermocouple structure for enzymatic reaction detection. Thermochim Acta. 2018;668:110–5.

    Article  CAS  Google Scholar 

  11. Fei R, Means AK, Abraham AA, Ak L, Coté GL, Grunlan MA. Self-cleaning, thermoresponsive P (NIPAAm-co-AMPS) double network membranes for implanted glucose biosensors. Macromol. Mater. Eng. 2016;301(8):935–43.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  12. Tian K, Nie F, Luo K, Zheng X, Zheng J. A sensitive electrochemiluminescence glucose biosensor based on graphene quantum dot prepared from graphene oxide sheets and hydrogen peroxide. J Electroanal Chem. 2017;801:162–70.

    Article  CAS  Google Scholar 

  13. Xiao Y, Xu L, Qi LW. Electrochemiluminescence bipolar electrode array for the multiplexed detection of glucose, lactate and choline based on a versatile enzymatic approach. Talanta. 2017;165:577–83.

    Article  CAS  PubMed  Google Scholar 

  14. Lisi F, Ariotti N, Bakthavathsalam P, Benedetti T, Tilley RD, Gooding JJ. The use of a personal glucose meter for detecting procalcitonin through glucose encapsulated within liposomes. Analyst. 2019;144(21):6225–30.

    Article  PubMed  Google Scholar 

  15. Chidri SV, Vidya G. Assessment of pulmonary functions in type 2 diabetes mellitus: its correlation with glycemic control and body mass index. Natl J Physiol Pharm Pharmacol. 2020;10(7):553–6.

    Article  Google Scholar 

  16. Thaler M, Luppa PB. Highly sensitive immunodiagnostics at the point of care employing alternative recognition elements and smartphones: hype, trend, or revolution? Anal Bioanal Chem. 2019:1–13.

  17. Farahani A, Sereshti H. An integrated microfluidic device for solid-phase extraction and spectrophotometric detection of opium alkaloids in urine samples. Anal Bioanal Chem. 2020;412(1):129–38.

    Article  CAS  PubMed  Google Scholar 

  18. Farahani A, Azimi S, Tajaddodi A, Docoslis A, Tashakori C. Screen-printed anion-exchange solid-phase extraction: a new strategy for point-of-care determination of angiotensin receptor blockers. Talanta. 2020;222:121518.

    Article  PubMed  Google Scholar 

  19. Mercer C, Bennett R, Conghaile PÓ, Rusling JF, Leech D. Glucose biosensor based on open-source wireless microfluidic potentiostat. Sensors Actuators B Chem. 2019;290:616–24.

    Article  CAS  Google Scholar 

  20. Gao J, Huang W, Chen Z, Yi C, Jiang L. Simultaneous detection of glucose, uric acid and cholesterol using flexible microneedle electrode array-based biosensor and multi-channel portable electrochemical analyzer. Sensors Actuators B Chem. 2019;287:102–10.

    Article  CAS  Google Scholar 

  21. Zarei M. Advances in point-of-care technologies for molecular diagnostics. Biosens Bioelectron. 2017;98:494–506.

    Article  CAS  PubMed  Google Scholar 

  22. Syedmoradi L, Daneshpour M, Alvandipour M, Gomez FA, Hajghassem H, Omidfar K. Point of care testing: the impact of nanotechnology. Biosens Bioelectron. 2017;87:373–87.

    Article  CAS  PubMed  Google Scholar 

  23. Farahani A, Sereshti H. Developing a point-of-care system for determination of dopamine, ascorbic and uric acids in biological fluids using a screen-printed electrode modified by three dimensional graphene/carbon nanotube hybrid. Int J Electrochem Sci. 2019;14:6195–208.

    Article  CAS  Google Scholar 

  24. Kumar S, Rani R, Dilbaghi N, Tankeshwar K, Kim KH. Carbon nanotubes: a novel material for multifaceted applications in human healthcare. Chem Soc Rev. 2017;46(1):158–96.

    Article  CAS  PubMed  Google Scholar 

  25. Chen J, Meng HM, An Y, Liu J, Yang R, Qu L, et al. A fluorescent nanosphere-based immunochromatography test strip for ultrasensitive and point-of-care detection of tetanus antibody in human serum. Anal Bioanal Chem. 2020;412(5):1151–8.

    Article  CAS  PubMed  Google Scholar 

  26. Pourahadi A, Farahani A, Hosseiny Davarani SS, Nojavan S, Tashakori C. Developing a miniaturized setup for in-tube simultaneous determination of three alkaloids using electromembrane extraction in combination with ultraviolet spectrophotometry. J Sep Sci. 2019;42(19):3126–33.

    Article  CAS  PubMed  Google Scholar 

  27. Wang C, Wang Y, Zhou Y, Wu ZQ, Xia XH. High-performance bioanalysis based on ion concentration polarization of micro-/nanofluidic devices. Anal Bioanal Chem. 2019:1–10.

  28. Yoon H, Nah J, Kim H, Ko S, Sharifuzzaman M, Barman SC, et al. A chemically modified laser-induced porous graphene based flexible and ultrasensitive electrochemical biosensor for sweat glucose detection. Sensors Actuators B Chem. 2020;311:127866.

    Article  CAS  Google Scholar 

  29. Bilal M, Zhao Y, Rasheed T, Iqbal HM. Magnetic nanoparticles as versatile carriers for enzymes immobilization: a review. Int J Biol Macromol. 2018;120:2530–44.

    Article  CAS  PubMed  Google Scholar 

  30. Farzin L, Shamsipur M. Recent advances in design of electrochemical affinity biosensors for low level detection of cancer protein biomarkers using nanomaterial-assisted signal enhancement strategies. J Pharm Biomed. 2018;147:185–210.

    Article  CAS  Google Scholar 

  31. Wang Z, Dai Z. Carbon nanomaterial-based electrochemical biosensors: an overview. Nanoscale. 2015;7(15):6420–31.

    Article  CAS  PubMed  Google Scholar 

  32. Yang R, Tang Z, Yan J, Kang H, Kim Y, Zhu Z, Tan W. Tan, Non-covalent assembly of carbon nanotubes and single-stranded DNA: an effective sensing platform for probing biomolecular interactions. Anal Chem 2008;80(19):7408–7413.

  33. Rawson FJ, Yeung CL, Jackson SK, Mendes PM. Tailoring 3D single-walled carbon nanotubes anchored to indium tin oxide for natural cellular uptake and intracellular sensing. Nano Lett. 2013;13(1):1–8.

    Article  CAS  PubMed  Google Scholar 

  34. Aydinli A, Yuksel R, Unalan HE. Vertically aligned carbon nanotube–Polyaniline nanocomposite supercapacitor electrodes. Int J Hydrog Energy. 2018;43(40):18617–25.

    Article  CAS  Google Scholar 

  35. Dogru IB, Durukan MB, Turel O, Unalan HE. Flexible supercapacitor electrodes with vertically aligned carbon nanotubes grown on aluminum foils. Prog Nat Sci. 2016;26(3):232–6.

    Article  CAS  Google Scholar 

  36. Wang X, Ugur A, Goktas H, Chen N, Wang M, Lachman N, et al. Room temperature resistive volatile organic compound sensing materials based on a hybrid structure of vertically aligned carbon nanotubes and conformal oCVD/iCVD polymer coating. ACS Sens. 2016;1(4):374–83.

    Article  CAS  Google Scholar 

  37. Azimi S, Farahani A, Sereshti H. Plasma-functionalized highly aligned CNT-based biosensor for point of care determination of glucose in human blood plasma. Electroanalysis. 2020;32(2):394–403.

    Article  CAS  Google Scholar 

  38. Lin Y, Lu F, Tu Y, Ren Z. Glucose biosensors based on carbon nanotube nanoelectrode ensembles. Nano Lett. 2004;4(2):191–5.

    Article  CAS  Google Scholar 

  39. Pumera M. The electrochemistry of carbon nanotubes: fundamentals and applications. Chem Eur. 2009;15(20):4970–8.

    Article  CAS  Google Scholar 

  40. Brownlee BJ, Bahari M, Harb JN, Claussen JC, Iverson BD. Electrochemical glucose sensors enhanced by methyl viologen and vertically aligned carbon nanotube channels. ACS Appl Mater Interfaces. 2018;10(34):28351–60.

    Article  CAS  PubMed  Google Scholar 

  41. Raphev VR, Henna TK, Nivitha KP, Mufeedha P, Sabu C, Pramod K. Advanced biomedical applications of carbon nanotube. Mater. Sci. Eng. C. 2019;100:616–30.

    Article  Google Scholar 

  42. Yang Y, Li M, Zhu Z. A novel electrochemical sensor based on carbon nanotubes array for selective detection of dopamine or uric acid. Talanta. 2019;201:295–300.

    Article  CAS  PubMed  Google Scholar 

  43. Komane PP, Kumar P, Choonara YE, Pillay V. Functionalized, vertically super-aligned multiwalled carbon nanotubes for potential biomedical applications. Int J Mol Sci. 2020;21(7):2276.

    Article  CAS  PubMed Central  Google Scholar 

  44. Varmira K, Mohammadi G, Mahmoudi M, Khodarahmi R, Rashidi K, Hedayati M, et al. Fabrication of a novel enzymatic electrochemical biosensor for determination of tyrosine in some food samples. Talanta. 2018;183:1–10.

    Article  CAS  PubMed  Google Scholar 

  45. Jiang H, Wei Z, Cai X, Lai L, Ma J, Haung W. A cathode for Li-ion batteries made of vanadium oxide on vertically aligned carbon nanotube arrays/graphene foam. Chem Eng J. 2019;359:1668–76.

    Article  CAS  Google Scholar 

  46. Ji D, Liu L, Li S, Chen C, Lu Y, Wu J, et al. Smartphone-based cyclic voltammetry system with graphene modified screen printed electrodes for glucose detection. Biosens Bioelectron. 2017;98:449–56.

    Article  CAS  PubMed  Google Scholar 

  47. Feng X, Cheng H, Pan Y, Zheng H. Development of glucose biosensors based on nanostructured graphene-conducting polyaniline composite. Biosens Bioelectron. 2015;70:411–7.

    Article  CAS  PubMed  Google Scholar 

  48. Ávila-Orta CA, Cruz-Delgado VJ, Neira-Velázquez MG, Hernández-Hernández E, Méndez-Padilla MG, Medellín-Rodríguez FJ. Surface modification of carbon nanotubes with ethylene glycol plasma. Carbon. 2009;47(8):1916–21.

    Article  Google Scholar 

  49. Akhtar MA, Batool R, Hayat A, Han D, Riaz S, Khan SU, et al. Functionalized graphene oxide bridging between enzyme and au-sputtered screen-printed interface for glucose detection. ACS Appl Nano Mater. 2019;2(3):1589–95.

    Article  CAS  Google Scholar 

  50. Phetsang S, Jakmunee J, Mungkornasawakul P, Laocharoensuk R, Ounnunkad K. Sensitive amperometric biosensors for detection of glucose and cholesterol using a platinum/reduced graphene oxide/poly (3-aminobenzoic acid) film-modified screen-printed carbon electrode. Bioelectrochemistry. 2019;127:125–35.

    Article  CAS  PubMed  Google Scholar 

  51. Jose MV, Marx S, Murata H, Koepsel RR, Russell AJ. Direct electron transfers in a mediator-free glucose oxidase-based carbon nanotube-coated biosensor. Carbon. 2012;50(11):4010–20.

    Article  CAS  Google Scholar 

  52. Soylemez S, Kaya HZ, Adum YA, Toppare L. A multipurpose conjugated polymer: electrochromic device and biosensor construction for glucose detection. Org Electron. 2019;65:327–33.

    Article  CAS  Google Scholar 

  53. Guan H, Gong D, Song Y, Han B, Zhang N. Biosensor composed of integrated glucose oxidase with liposome microreactors/chitosan nanocomposite for amperometric glucose sensing. Colloids Surf A Physicochem Eng Asp. 2019;574:260–7.

    Article  CAS  Google Scholar 

  54. Al-Sagur H, Komathi S, Khan MA, Gurek AG, Hassan A. A novel glucose sensor using lutetium phthalocyanine as redox mediator in reduced graphene oxide conducting polymer multifunctional hydrogel. Biosens Bioelectron. 2017;92:638–45.

    Article  CAS  PubMed  Google Scholar 

  55. Chen C, Ran R, Yang Z, Lv R, Shen W, Kang F, et al. An efficient flexible electrochemical glucose sensor based on carbon nanotubes/carbonized silk fabrics decorated with Pt microspheres. Sens Actuators B Chem. 2018;256:63–70.

    Article  CAS  Google Scholar 

  56. Senel M. Simple method for preparing glucose biosensor based on in-situ polypyrrole cross-linked chitosan/glucose oxidase/gold bionanocomposite film. Mater Sci Eng C. 2015;48:287–93.

    Article  CAS  Google Scholar 

  57. Savk A, Aydin H, Cellat K, Sen F. A novel high performance non-enzymatic electrochemical glucose biosensor based on activated carbon-supported Pt-Ni nanocomposite. J Mol Liq. 2020;300:112355.

    Article  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Chemical Engineering, Queen’s University, Kingston, ON, K7L 3N6, Canada

    Shamim Azimi & Aristides Docoslis

  2. Nanobioelectronics Lab, School of Chemistry, College of Science, University of Tehran, Tehran, 1748714176, Iran

    Ali Farahani

  3. Department of Chemical Engineering, Faculty of Engineering, University of Tehran, Tehran, 1438615995, Iran

    Sahar Vahdatifar

Authors
  1. Shamim Azimi
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Ali Farahani
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Aristides Docoslis
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Sahar Vahdatifar
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Ali Farahani.

Ethics declarations

Conflict of interest

The authors declare that they have no conflicts of interest.

Informed consent

The human plasma samples were obtained from healthy and diabetic patient volunteers with informed consent to the Iranian Blood Transfusion Organization (Tehran, Iran). The studies have been performed in accordance with the ethical standards approved by the appropriate research ethics committee of the University of Tehran.

Additional information

Publisher’s note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Supplementary information

ESM 1

(PDF 1073 kb)

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Azimi, S., Farahani, A., Docoslis, A. et al. Developing an integrated microfluidic and miniaturized electrochemical biosensor for point of care determination of glucose in human plasma samples. Anal Bioanal Chem 413, 1441–1452 (2021). https://doi.org/10.1007/s00216-020-03108-3

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00216-020-03108-3

Keywords

Search

Navigation