Skip to main content
SpringerLink
Log in

Integrated microfluidic system for electrochemical sensing of glycosylated hemoglobin

  • Research Paper
  • Published:
Microfluidics and Nanofluidics Aims and scope Submit manuscript

Abstract

This article reports a new miniature electrochemical detection system integrating a sample pretreatment device for fast detection of glycosylated hemoglobin (HbA1C), which is a common indicator for diabetes mellitus. In this system, circular micropumps, normally closed microvalves, dielectrophoretic (DEP) electrodes, and electrochemical sensing electrode are integrated to perform several crucial processes. These processes include separation of red blood cells (RBCs), sample/reagent transportation, mixing, cell lysis, and electrochemical sensing. For the HbA1C measurement, the RBCs are separated and are collected from whole human blood by using a positive DEP force generated by the DEP electrodes. The collected RBCs are then lysed to release HbA1C for the subsequent electrochemical detection processes. Experimental data show that the RBCs are successfully separated and are collected using the developed system with a RBCs capture rate of 84.2%. The subsequent detection of HbA1C is automatically completed by utilizing electrochemical sensing electrode. The microfluidic system only consumes a sample volume of 200 μl. The entire process is automatically performed within a short period of time (10 min). The development of this integrated microfluidic system may be promising for the clinical monitoring of diabetes mellitus.

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
Fig. 9
Fig. 10

Similar content being viewed by others

Abbreviations

AC:

Alternating current

Au:

Gold

Ag:

Silver

CCD:

Charge-coupled device

CNC:

Computer numerical control

CV:

Cyclic voltammetry

DEP:

Dielectrophoretic

DM:

Diabetes mellitus

DI:

Deionized

DMEM:

Dulbecco’s modified eagle medium

EMV:

Electromagnetic valve

FcBA:

Ferroceneboronic acid

Hb:

Hemoglobin

HbA1C :

Glycosylated hemoglobin

MEMS:

Micro-electro-mechanical-systems

PBS:

Phosphate-buffered saline

PDMS:

Polydimethylsiloxane

PMMA:

Polymethylmethacrylate

Pt:

Platinum

RBCs:

Red blood cells

Ti:

Titanium

Vp-p:

Peak-to-peak voltage

WBCs:

White blood cells

References

  • Braschler T, Demierre N, Nascimento E, Silva T, Olivab AG, Renaud P (2008) Continuous separation of cells by balanced dielectrophoretic forces at multiple frequencies. Lab Chip 8:280–286

    Article  Google Scholar 

  • Bunn HF, Haney DN, Gabbay KH, Gallop PM (1975) Further identification of the nature and linkage of the carbohydrate in hemoglobin A1c. Biochem Biophys Res Commun 67:103–109

    Article  Google Scholar 

  • Chen DF, Du H (2007) A dielectrophoretic barrier-based microsystem for separation of microparticles. Microfluid Nanofluid 3:603–610

    Article  Google Scholar 

  • Chen DF, Du H, Li WH (2006) A 3D paired microelectrode array for accumulation and separation of microparticles. J Micromech Microeng 16:1162–1169

    Article  Google Scholar 

  • Chuang SH (2009) Using a N-(1-deoxy-D-fructopyranos-1-yl)-L-valine imprinted polymer as the recognition cavities for the target molecule to fabricate HbA1c biosensor. Dissertation, National Cheng Kung University

  • Flückiger R, Winterhalter KH (1976) In vitro synthesis of hemoglobin A1c. FEBS Lett 71:356–360

    Article  Google Scholar 

  • Goldstein DE, Little RR, Wiedmeyer HM, England JD, McKenzie EM (1986) Glycated hemoglobin-methodologies and clinical applications. Clin Chem 32:B64–B70

    Google Scholar 

  • Grodzinski P, Liu R, Yang J, Ward MD (2004) Microfluidic system integration in sample preparation chip-sets-a summary. In: Proceedings of the 26th annual international conference of the IEEE EMBS, pp 2615–2618

  • Hageman J, Kuehn G (1977) Assay of adenylate-cyclase by use of polyacrylamide-boronate gel columns. Anal Biochem 80:547–554

    Article  Google Scholar 

  • Huang Y, Ewalt KL, Tirado M, Haigis R, Forster A, Ackley D, Heller MJ, O’Connel JP, Krihak M (2001) Electric manipulation of bioparticles and macromolecules on microfabricated electrodes. Anal Chem 73:1549–1559

    Article  Google Scholar 

  • Huang CJ, Lu CC, Lin TY, Chou TC, Lee GB (2007a) An electrochemical albumin-sensing system utilizing microfluidic technology. J Micromech Microeng 17:835–842

    Article  Google Scholar 

  • Huang CJ, Chen YH, Wang CH, Chou TC, Lee GB (2007b) Integrated microfluidic systems for automatic glucose sensing and insulin injection. Sens Actuators B 122:461–468

    Article  Google Scholar 

  • Jeppsson JO, Kobold U, Barr J et al (2002) Approved IFCC reference method for the measurement of HbA1c in human blood. Clin Chem Lab Med 40:78–89

    Article  Google Scholar 

  • John WG (1997) Glycated haemoglobin analysis. Ann Clin Biochem 34:17–31

    Google Scholar 

  • John WG (2003) Haemoglobin A1c: analysis and standardization. Clin Chem Lab Med 41:1199–1212

    Article  Google Scholar 

  • Jones TB (1995) Electromechanics of particles. Cambridge University Press, New York

    Book  Google Scholar 

  • Lin YH, Lee GB (2008) Optically induced flow cytometry for continuous microparticle counting and sorting. Biosens Bioelectron 24:572–578

    Article  Google Scholar 

  • Liu S, Wollenberger U, Katterle M, Scheller FW (2006) Ferroceneboronic acid-based amperometric biosensor for glycated hemoglobin. Sens Actuators B 113:623–629

    Article  Google Scholar 

  • Marko-varga G, Emneus J, Gorton L, Ruzgas T (1995) Development of enzyme-based amperometric sensors for the determination of phenolic-compounds. TRAC (Trends Anal Chem) 14:319–328

    Google Scholar 

  • Ogawa K, Stöllner D, Scheller F, Warsinke A, Ishimura F, Tsugawa W, Ferri S, Sode K (2002) Development of a flow-injection analysis (FIA) enzyme sensor for fructosyl amine monitoring. Anal Bioanal Chem 373:211–214

    Article  Google Scholar 

  • Pethig R, Markx GH (1997) Applications of dielectrophoresis in biotechnology. Trends Biotechnol 15:426–432

    Article  Google Scholar 

  • Pohl HA (1978) Dielectrophoresis. Cambridge University Press, Cambridge, UK

    Google Scholar 

  • Sode K, Takahashi Y, Ohta S, Tsugawa W, Yamazaki T (2001) A new concept for the construction of an artificial dehydrogenase for fructosylamine compounds and its application for an amperometric fructosylamine sensor. Anal Chim Acta 435:151–156

    Article  Google Scholar 

  • Stollner D, Stocklein W, Scheller F, Warsinke A (2002) Membrane-immobilized haptoglobin as affinity matrix for a hemoglobin-A1c immunosensor. Anal Chim Acta 470:111–119

    Article  Google Scholar 

  • Tai CH, Hsiung SK, Chen CY, Tsai ML, Lee GB (2007) Automatic microfluidic platform for cell separation and nucleus collection. Biomed Microdevices 9:533–543

    Article  Google Scholar 

  • Tseng HY, Wang CH, Lin WY, Lee GB (2007) Membrane-activated microfluidic rotary devices for pumping and mixing. Biomed Microdevices 9:545–554

    Article  Google Scholar 

  • Turner APF, Chen B, Piletsky SA (1999) In vitro diagnostics in diabetes: meeting the challenge. Clin Chem 45:1596–1601

    Google Scholar 

  • Urdaneta M, Smela E (2008) The design of dielectrophoretic flow-through sorters using a figure of merit. J Micromech Microeng 18:1–8

    Article  Google Scholar 

  • Wang J (1999) Amperometric biosensors for clinical and therapeutic drug monitoring: a review. J Pharm Biomed Anal 19:47–53

    Article  Google Scholar 

  • Wang XB, Huang Y, Becker FF, Gascoyne PRC (1994) A unified theory of dielectrophoresis and travelling wave dielectrophoresis. J Phys D Appl Phys 27:1571–1574

    Article  Google Scholar 

  • Wang L, Flanaganb LA, Jeona NL, Monukib E, Lee AP (2007) Dielectrophoresis switching with vertical sidewall electrodes for microfluidic flow cytometry. Lab Chip 7:1114–1120

    Article  Google Scholar 

  • Wilson DH, Bogacz JP, Forsythe CM, Turk PJ, Lane TL, Gates RC, Brandt DR (1993) Fully automated assay of glycohemoglobin with the Abbott lMx® analyzer: novel approaches for separation and detection. Clin Chem 39:2090–2097

    Google Scholar 

  • Yang SY, Lin JL, Lee GB (2009a) A vortex-type micromixer utilizing pneumatic-driven membranes. J Micromech Microeng 19. Article Number: 035020

  • Yang YN, Hsiung SK, Lee GB (2009b) A pneumatic micropump incorporated with a normally closed valve capable of generating a high pumping rate and a high back pressure. Microfluid Nanofluid 6:823–833

    Article  Google Scholar 

Download references

Acknowledgments

The authors gratefully acknowledge the financial support provided to this study by the National Science Council in Taiwan (NSC 96-2120-M-006-008 and NSC 97-2120-M-006-007). This study is also partially supported by the Ministry of Education, Taiwan under the NCKU Project for Promoting Academic Excellence & Developing World Class—search Centers.

Author information

Authors and Affiliations

  1. Department of Engineering Science, National Cheng Kung University, Tainan 701, Taiwan, ROC

    Chao-June Huang & Gwo-Bin Lee

  2. Department of Chemical Engineering, National Cheng Kung University, Tainan 701, Taiwan, ROC

    Hui-Ching Chien

  3. Department of Chemical Engineering, Tatung University, Taipei 104, Taiwan, ROC

    Tse-Chuan Chou

Authors
  1. Chao-June Huang
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Hui-Ching Chien
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Tse-Chuan Chou
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Gwo-Bin Lee
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Gwo-Bin Lee.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Huang, CJ., Chien, HC., Chou, TC. et al. Integrated microfluidic system for electrochemical sensing of glycosylated hemoglobin. Microfluid Nanofluid 10, 37–45 (2011). https://doi.org/10.1007/s10404-010-0644-x

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s10404-010-0644-x

Keywords

Search

Navigation