Skip to main content
Top
Published in: Journal of Cancer Research and Clinical Oncology 11/2011

01-11-2011 | Rapid Communication

Microelectromechanical system-based diagnostic technology for cervical cancer

Authors: Song Gao, Xinyan Wang

Published in: Journal of Cancer Research and Clinical Oncology | Issue 11/2011

Login to get access

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.
Literature
go back to reference Alon R, Hammer DA, Springer TA (1995) Lifetime of the P-selectin-carbohydrate bond and its response to tensile force in hydrodynamic flow. Nature 374:539–542PubMedCrossRef Alon R, Hammer DA, Springer TA (1995) Lifetime of the P-selectin-carbohydrate bond and its response to tensile force in hydrodynamic flow. Nature 374:539–542PubMedCrossRef
go back to reference Breitburd Francoise CP (1999) Human papillomavirus vaccines. Semin Cancer Biol 9:431–445CrossRef Breitburd Francoise CP (1999) Human papillomavirus vaccines. Semin Cancer Biol 9:431–445CrossRef
go back to reference 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 72:3253–3259PubMedCrossRef 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 72:3253–3259PubMedCrossRef
go back to reference Esch MB, Locascio LE, Tarlov MJ, Durst RA (2001) Detection of viable cryptosporidium parvum using DNA-modified liposomes in a microfluidic chip. Anal Chem 73:2952–2958PubMedCrossRef Esch MB, Locascio LE, Tarlov MJ, Durst RA (2001) Detection of viable cryptosporidium parvum using DNA-modified liposomes in a microfluidic chip. Anal Chem 73:2952–2958PubMedCrossRef
go back to reference 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 71:2449–2456PubMed 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 71:2449–2456PubMed
go back to reference 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 236:76–85CrossRef 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 236:76–85CrossRef
go back to reference 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 2:207–214CrossRef 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 2:207–214CrossRef
go back to reference Giroglou T, Florin L, Schafer F, Streeck RE, Sapp M (2001) Human papillomavirus infection requires cell surface heparan sulfate. J Virol 75:1565–1570PubMedCrossRef Giroglou T, Florin L, Schafer F, Streeck RE, Sapp M (2001) Human papillomavirus infection requires cell surface heparan sulfate. J Virol 75:1565–1570PubMedCrossRef
go back to reference Hausen HZ (1999) Papillomaviruses in human cancers. Proc Assoc Am Physicians 111:1–7CrossRef Hausen HZ (1999) Papillomaviruses in human cancers. Proc Assoc Am Physicians 111:1–7CrossRef
go back to reference Hausen HZ (2000) Papillomaviruses causing cancer: evasion from host-cell control in early events in carcinogenesis. J Natl Cancer Inst 92:690–698PubMedCrossRef Hausen HZ (2000) Papillomaviruses causing cancer: evasion from host-cell control in early events in carcinogenesis. J Natl Cancer Inst 92:690–698PubMedCrossRef
go back to reference 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 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
go back to reference Makamba H, Kim JH, Lim K, Park N, Hahn JH (2003) Surface modification of polydimethylsiloxane microchannels. Electrophoresis 24:3607–3619PubMedCrossRef Makamba H, Kim JH, Lim K, Park N, Hahn JH (2003) Surface modification of polydimethylsiloxane microchannels. Electrophoresis 24:3607–3619PubMedCrossRef
go back to reference 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 77:1120–1124PubMedCrossRef 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 77:1120–1124PubMedCrossRef
go back to reference McDonald JC, Duffy DC, Anderson JR, Chiu DT, Wu H, Whitesides GM et al (2000) Fabrication of microfluidic systems in polydimethylsiloxane. Electrophoresis 21:27–40PubMedCrossRef McDonald JC, Duffy DC, Anderson JR, Chiu DT, Wu H, Whitesides GM et al (2000) Fabrication of microfluidic systems in polydimethylsiloxane. Electrophoresis 21:27–40PubMedCrossRef
go back to reference N’Dri NA, Shyy W, Tran-Son-Tay R (2003) Computational modeling of cell adhesion and movement using a continuum-kinetics approach. Biophys J 85:2273–2286PubMedCrossRef N’Dri NA, Shyy W, Tran-Son-Tay R (2003) Computational modeling of cell adhesion and movement using a continuum-kinetics approach. Biophys J 85:2273–2286PubMedCrossRef
go back to reference 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 65:121–129PubMedCrossRef 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 65:121–129PubMedCrossRef
go back to reference Pollock RR, French DL, Gefter ML, Scharff MD (1988) Identification of mutant monoclonal antibodies with increased antigen binding. Proc Natl Acad Sci 85:2298–2302PubMedCrossRef Pollock RR, French DL, Gefter ML, Scharff MD (1988) Identification of mutant monoclonal antibodies with increased antigen binding. Proc Natl Acad Sci 85:2298–2302PubMedCrossRef
go back to reference Rabbany SY, Kusterbeck AW, Bredehorst R, Ligler FS (1994) Effect of antibody density on the displacement kinetics of a flow immunoassay. J Immunol Methods 168:227–234PubMedCrossRef Rabbany SY, Kusterbeck AW, Bredehorst R, Ligler FS (1994) Effect of antibody density on the displacement kinetics of a flow immunoassay. J Immunol Methods 168:227–234PubMedCrossRef
go back to reference Risendal BDJ, Fowler B, Papenfuss M, Giuliano A (1999) Pap smear screening among urban southwestern American Indian women. Prev Med 29:510–518PubMedCrossRef Risendal BDJ, Fowler B, Papenfuss M, Giuliano A (1999) Pap smear screening among urban southwestern American Indian women. Prev Med 29:510–518PubMedCrossRef
go back to reference Sia Samuel K, Whitesides GM (2003) Microfluidic devices fabricated in polydimethylsiloxane for biological studies. Electrophoresis 24:3563–3576PubMedCrossRef Sia Samuel K, Whitesides GM (2003) Microfluidic devices fabricated in polydimethylsiloxane for biological studies. Electrophoresis 24:3563–3576PubMedCrossRef
go back to reference Stromberg A, Karlsson A, Ryttsen F, Davidson M, Chiu DT, Orwar O (2001) Microfluidic device for combinatorial fusion of liposomes and cells. Anal Chem 73:126–130PubMedCrossRef Stromberg A, Karlsson A, Ryttsen F, Davidson M, Chiu DT, Orwar O (2001) Microfluidic device for combinatorial fusion of liposomes and cells. Anal Chem 73:126–130PubMedCrossRef
go back to reference Zhao B, Viernes NOL, Moore JS, Beebe DJ (2002) Control and applications of immiscible liquids in microchannels. J Am Chem Soc 124:5284–5285PubMedCrossRef Zhao B, Viernes NOL, Moore JS, Beebe DJ (2002) Control and applications of immiscible liquids in microchannels. J Am Chem Soc 124:5284–5285PubMedCrossRef
go back to reference 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 60:7008–7013PubMed 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 60:7008–7013PubMed
Metadata
Title
Microelectromechanical system-based diagnostic technology for cervical cancer
Authors
Song Gao
Xinyan Wang
Publication date
01-11-2011
Publisher
Springer-Verlag
Published in
Journal of Cancer Research and Clinical Oncology / Issue 11/2011
Print ISSN: 0171-5216
Electronic ISSN: 1432-1335
DOI
https://doi.org/10.1007/s00432-011-1019-8

Other articles of this Issue 11/2011

Journal of Cancer Research and Clinical Oncology 11/2011 Go to the issue