Skip to main content
SpringerLink
Log in

Concentration-enhanced rapid detection of human chorionic gonadotropin as a tumor marker using a nanofluidic preconcentrator

  • Short Communication
  • Published:
Microfluidics and Nanofluidics Aims and scope Submit manuscript

Abstract

Here, we report a new method of concentration-enhanced binding kinetics for a rapid immunoassay screening test on a gold surface in a poly(dimethylsiloxane) (PDMS) microfluidic chip format. The use of alkylthiolate self-assembled monolayers on gold surfaces of a PDMS-glass microchip resulted in accelerated binding kinetics at an electrokinetic trapping zone. We used human chorionic gonadotropin (hCG) as a model analyte for a tumor marker to demonstrate the potential ability of dynamic preconcentrating operation in serum using 1D planar gold surface and demonstrated concentration-enhanced binding kinetics by 500-fold. The preconcentration of cy3 labeled streptavidin onto biotinylated Au surface also revealed that the binding kinetics of the protein were linearly proportional to the concentration profile of the preconcentration plug. We showed rapid detection of hCG in the clinical range with a shorten total assay time of 15 min. The enhanced binding kinetics between hCG antigen-antibody via preconcentration showed good feasibility for use in a rapid immunoassay screening test.

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

References

  • Andrade J (1985) Surface and interfacial aspects of biomedical polymers. Pelnum Press, New York

    Google Scholar 

  • Badia A, Demers L, Dickinson L, Morin FG, Lennox RB, Reven L (1997) Gold-sulfur interactions in alkylthiol self-assembled monolayers formed on gold nanoparticles studied by solid-state NMR. J Am Chem Soc 119(45):11104–11105

    Article  Google Scholar 

  • Canaria CA, So J, Maloney JR, Yu CJ, Smith JO, Roukes ML, Fraser SE, Lansford R (2006) Formation and removal of alkylthiolate self-assembled monolayers on gold in aqueous solutions. Lab Chip 6:289–295

    Article  Google Scholar 

  • Cesaro-Tadic S, Dernick G, Juncker D, Buurman G, Kropshofer H, Michel B, Fattinger C, Delamarche E (2004) High-sensitivity miniaturized immunoassays for tumor necrosis factor using microfluidic systems. Lab Chip 4:563–569

    Article  Google Scholar 

  • Cole LA (1997) Immunoassay of human chorionic gonadotropin, its free subunits, and metabolites. Clin Chem 43:2233–2243

    Google Scholar 

  • Cui Y, Wei Q, Park H, Lieber CM (2001) Nanowire nanosensors for highly sensitive and selective detection of biological and chemical species. Science 293(5533):1289–1292

    Article  Google Scholar 

  • de Mol NJ, Plomp E, Fischer MJE, Ruijtenbeek R (2000) Kinetic analysis of the mass transport limited interaction between the tyrosine kinase lck SH2 domain and a phosphorylated peptide studied by a new cuvette-based surface plasmon resonance instrument. Anal Biochem 279(1):61–70

    Article  Google Scholar 

  • Dubois LH, Nuzzo RG (1992) Synthesis, structure and properties of model organic surfaces. Annu Rev Phys Chem 43:437–463

    Google Scholar 

  • Gong P, Lee C-Y, Gamble LJ, Castner DG, Grainger DW (2006) Hybridization behavior of mixed DNA/alkylthiol monolayers on gold: characterization by surface plasmon resonance and 32P radiometric assay. Anal Chem 78:3326–3334

    Article  Google Scholar 

  • Green NM (1990) Avidin and streptavidin. Methods Enzymol 184:51–67

    Article  Google Scholar 

  • Harder P, Grunze M, Dahint R, Whitesides GM, Laibinis PE (1998) Molecular conformation in oligo(ethylene glycol)-terminated self-assembled monolayers on gold and silver surfaces determines their ability to resist protein adsorption. J Phys Chem B 102:426–436

    Article  Google Scholar 

  • Kim SJ, Wang Y-C, Lee JH, Jang H, Han J (2007) Concentration polarization and nonlinear electrokinetic flow near a nanofluidic channel. Phys Rev Lett 99:044501

    Article  Google Scholar 

  • Kukanskis K, Elkind J, Melendez J, Murphy T, Miller G, Garner H (1999) Anal Biochem 274:7–17

    Article  Google Scholar 

  • Kurman RJ, Scardino PT, McIntire KR, Waldmann TA, Javadpour N (1977) Cellular localization of alpha-fetoprotein and human chorionic gonadotropin in germ cell tumors of the testis using an indirect immunoperoxidase technique. A new approach to classification utilizing tumor markers. Cancer 40(5):2136–2151

    Article  Google Scholar 

  • Lang HP, Baller MK, Berger R, Gerberc C, Gimzewski JK, Battiston FM, Fornaro P, Ramseyer JP, Meyer E, Güntherodt HJ (1999) An artificial nose based on a micromechanical cantilever array. Anal Chim Acta 393(1–3):59–65

    Article  Google Scholar 

  • Lee JH, Hwang KS, Park J, Yoon KH, Yoon DS, Kim TS (2005) Immunoassay of prostate-specific antigen (PSA) using resonant frequency shift of piezoelectric nanomechanical microcantilever. Biosens Bioelectron 20(10):2157–2162

    Article  Google Scholar 

  • Lee JH, Chung S, Kim SJ, Han J (2007) Poly(dimethylsiloxane)-based protein preconcentration using a nanogap generated by junction gap breakdown. Anal Chem 79(17):6868–6873

    Article  Google Scholar 

  • Lee JH, Song Y-A, Han J (2008) Multiplexed proteomic sample preconcentration device using surface-patterned ion-selective membrane. Lab Chip 8(4):596–601

    Article  Google Scholar 

  • Lempiainen A, Stenman U-H, Blomqvist C, Hotakainen K (2008) Free {beta}-subunit of human chorionic gonadotropin in serum is a diagnostically sensitive marker of seminomatous testicular cancer. Clin Chem 54(11):1840–1843

    Article  Google Scholar 

  • Mann K, Karl H-J (1983) Molecular heterogeneity of human chorionic gonadotropin and its subunits in testicular cancer. Cancer 52(4):654–660

    Article  Google Scholar 

  • Mock P, Kovalevskaya G, O’Connor JF, Campana A (2000) Choriocarcinoma-like human chorionic gonadotrophin (HCG) and HCG bioactivity during the first trimester of pregnancy. Human Reprod 15(10):2209–2214

    Article  Google Scholar 

  • Moulton HM, Yoshihara PH, Mason DH, Iversen PL, Triozzi PL (2002) Active specific immunotherapy with a ß-human chorionic gonadotropin peptide vaccine in patients with metastatic colorectal cancer. Clin Cancer Res 8:2044–2051

    Google Scholar 

  • Nair PR, Alam MA (2006) Performance limits of nanobiosensors. Appl Phys Lett 88:233120

    Article  Google Scholar 

  • Roche EJ, Pineri M, Duplessix R, Levelut AM (1981) J Polym Sci Polym Phys Ed 19:1

    Google Scholar 

  • Ulman A (1991) An introduction to ultrathin organic films: from Langmuir-Blodgett to self-assembly. Academic Press, Boston

    Google Scholar 

  • Wang Y-C, Han J (2008) Pre-binding dynamic range and sensitivity enhancement for immuno-sensors using nanofluidic preconcentrator. Lab Chip 8:392–394

    Article  Google Scholar 

  • Wang YC, Stevens AL, Han J (2005) Million-fold preconcentration of proteins and peptides by nanofluidic filter. Anal Chem 77:4293–4299

    Article  Google Scholar 

  • Weber PC, Ohlendorf DH, Wendoloski JJ, Salemme FR (1989) Structural origins of high-affinity biotin binding to streptavidin. Science 243(4887):85–88

    Article  Google Scholar 

Download references

Acknowledgments

This work was supported by NIH (CA119402). J. H. Lee is partially supported by the Research Grant of Kwangwoon University in 2010.

Author information

Authors and Affiliations

  1. Department of Electrical Engineering, Kwangwoon University, 447-1, Wolgye, Nowon, Seoul, 139-701, South Korea

    Jeong Hoon Lee

  2. Departments of Electrical Engineering and Computer Science, and Biological Engineering, Massachusetts Institute of Technology, Cambridge, MA, 02139, USA

    Jongyoon Han

Authors
  1. Jeong Hoon Lee
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Jongyoon Han
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Jongyoon Han.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Lee, J.H., Han, J. Concentration-enhanced rapid detection of human chorionic gonadotropin as a tumor marker using a nanofluidic preconcentrator. Microfluid Nanofluid 9, 973–979 (2010). https://doi.org/10.1007/s10404-010-0598-z

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s10404-010-0598-z

Keywords

Search

Navigation