Skip to main content
Log in

Microelectromechanical system-based diagnostic technology for cervical cancer

  • Rapid Communication
  • Published:
Journal of Cancer Research and Clinical Oncology Aims and scope Submit manuscript

Abstract

Purpose

To determine the correlations of human papillomavirus (HPV) infection and α6 integrin up-regulation to the tumorigenesis and development of cervical cancer, and develop an on-chip antibody-based detection system using the microelectromechanical system (MEMS) device for recognizing and capturing cervical cancer cells from a mixed cell population.

Methods

We determined the efficiency of an antibody-based MEMS platform in recognizing and capturing cervical cancer cells. In addition, α6 integrin was used as a capture antibody bound to the channel surface. Channels 2 cm long × 50 cm wide with inlet and outlet diameters of 50 cm were formed in microfluidic polydimethylsiloxane (PDMS) chips.

Results

The overall chip measured 2 cm × 1.5 cm × 0.5 cm. Using a syringe micropump, 20,000 normal human cervical epithelial cells (HCEC), 20,000 human cervical stromal cells (HCSC), and 20,000 human cervical cancer cells (HCCC) were suspended in PBS and flowed through the system at a rate of 20 mL/min. At this flow rate, more than 45% of cancer cells were captured, whereas less than 5% of normal cells were captured. In addition, we confirmed the specificity of this system in cell-type targeting using PCR.

Conclusions

MEMS is a sensitive and accurate method for capturing and enriching cells of interest. This technique is potentially useful in detecting cervical cancer at all stages, as well as other cancers with similar characteristics of cell surface antigen expression.

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

Access this article

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

Instant access to the full article PDF.

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5

References

  • Alon R, Hammer DA, Springer TA (1995) Lifetime of the P-selectin-carbohydrate bond and its response to tensile force in hydrodynamic flow. Nature 374:539–542

    Article  PubMed  CAS  Google Scholar 

  • Blawas AS, Reichert WM (1998) Biomaterials-protein patterning. Biomaterials 19:595–609

    Article  PubMed  CAS  Google Scholar 

  • Breitburd Francoise CP (1999) Human papillomavirus vaccines. Semin Cancer Biol 9:431–445

    Article  Google Scholar 

  • Brooks SA, Dontha N, Davis CB, Stuart JK, O’Neill G, Kuhr WG (2000) Segregation of micrometer-dimension biosensor elements on a variety of substrate surfaces. Anal Chem 72:3253–3259

    Article  PubMed  CAS  Google Scholar 

  • Esch MB, Locascio LE, Tarlov MJ, Durst RA (2001) Detection of viable cryptosporidium parvum using DNA-modified liposomes in a microfluidic chip. Anal Chem 73:2952–2958

    Article  PubMed  CAS  Google Scholar 

  • Evander M, Frazer IH, Payne E, Qi YM, Hengst K, McMillan NAJ (1997) Identification of the α6 Integrin as a candidate receptor for papillomaviruses. J Virol 71:2449–2456

    PubMed  CAS  Google Scholar 

  • Falcioni Rita AA, Nistico P, Stefano SD, Crescenzi M, Natali PG et al (1997) α6β4 and α6β1 integrins associate with ErbB-2 in human carcinoma cell lines. Exp Cell Res 236:76–85

    Article  Google Scholar 

  • Folch A, Mezzour S, During M, Hurtado O, Toner M, Muller R (2000) Stacks of microfabricated structures as scaffolds for cell culture and tissue engineering. Biochemical Microdevices 2:207–214

    Article  Google Scholar 

  • Giroglou T, Florin L, Schafer F, Streeck RE, Sapp M (2001) Human papillomavirus infection requires cell surface heparan sulfate. J Virol 75:1565–1570

    Article  PubMed  CAS  Google Scholar 

  • Hausen HZ (1999) Papillomaviruses in human cancers. Proc Assoc Am Physicians 111:1–7

    Article  Google Scholar 

  • Hausen HZ (2000) Papillomaviruses causing cancer: evasion from host-cell control in early events in carcinogenesis. J Natl Cancer Inst 92:690–698

    Article  PubMed  Google Scholar 

  • Jo B-H, Beebe DJ (1999) Fabrication of three-dimensional microfluidic systems by stacking molded polydimethylsiloxane (PDMS) layers. Part of the SPIE conference on microfluidic devices and Systems II 3877:0277–02786

  • Makamba H, Kim JH, Lim K, Park N, Hahn JH (2003) Surface modification of polydimethylsiloxane microchannels. Electrophoresis 24:3607–3619

    Article  PubMed  CAS  Google Scholar 

  • Marshak-Rothstein A, Siekevitz M, Margolies MN, Mudgett-Hunter M, Gefter ML (1980) Hybridoma proteins expressing the predominant idiotype of the antiazophenylarsonate response of A/J mice. Proc Natl Acad Sci 77:1120–1124

    Article  PubMed  CAS  Google Scholar 

  • McDonald JC, Duffy DC, Anderson JR, Chiu DT, Wu H, Whitesides GM et al (2000) Fabrication of microfluidic systems in polydimethylsiloxane. Electrophoresis 21:27–40

    Article  PubMed  CAS  Google Scholar 

  • N’Dri NA, Shyy W, Tran-Son-Tay R (2003) Computational modeling of cell adhesion and movement using a continuum-kinetics approach. Biophys J 85:2273–2286

    Article  PubMed  Google Scholar 

  • Park JS, Hwang ES, Nie PS, Kyung AH, Jong US, Joo KC et al (1997) Physical status and expression of HPV genes in cervical cancers. Gynecol Oncol 65:121–129

    Article  PubMed  CAS  Google Scholar 

  • Pollock RR, French DL, Gefter ML, Scharff MD (1988) Identification of mutant monoclonal antibodies with increased antigen binding. Proc Natl Acad Sci 85:2298–2302

    Article  PubMed  CAS  Google Scholar 

  • Rabbany SY, Kusterbeck AW, Bredehorst R, Ligler FS (1994) Effect of antibody density on the displacement kinetics of a flow immunoassay. J Immunol Methods 168:227–234

    Article  PubMed  CAS  Google Scholar 

  • Risendal BDJ, Fowler B, Papenfuss M, Giuliano A (1999) Pap smear screening among urban southwestern American Indian women. Prev Med 29:510–518

    Article  PubMed  CAS  Google Scholar 

  • Sia Samuel K, Whitesides GM (2003) Microfluidic devices fabricated in polydimethylsiloxane for biological studies. Electrophoresis 24:3563–3576

    Article  PubMed  CAS  Google Scholar 

  • Stromberg A, Karlsson A, Ryttsen F, Davidson M, Chiu DT, Orwar O (2001) Microfluidic device for combinatorial fusion of liposomes and cells. Anal Chem 73:126–130

    Article  PubMed  CAS  Google Scholar 

  • Zhao B, Viernes NOL, Moore JS, Beebe DJ (2002) Control and applications of immiscible liquids in microchannels. J Am Chem Soc 124:5284–5285

    Article  PubMed  CAS  Google Scholar 

  • Zuckier LS, Berkowitz EZ, Sattenberg RJ, Zhao QH, Deng HF, Scharff MD (2000) Influence of affinity and antigen density on antibody localization in a modifiable tumor targeting model. Cancer Res 60:7008–7013

    PubMed  CAS  Google Scholar 

Download references

Conflict of interest

We declared that there was no conflict of interest.

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Song Gao.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Gao, S., Wang, X. Microelectromechanical system-based diagnostic technology for cervical cancer. J Cancer Res Clin Oncol 137, 1721–1727 (2011). https://doi.org/10.1007/s00432-011-1019-8

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00432-011-1019-8

Keywords

Navigation