Skip to main content

Advertisement

Log in

Characterization of cell seeding and specific capture of B cells in microbubble well arrays

  • Published:
Biomedical Microdevices Aims and scope Submit manuscript

Abstract

Development of micro-well array systems for use in high-throughput screening of rare cells requires a detailed understanding of the factors that impact the specific capture of cells in wells and the distribution statistics of the number of cells deposited into wells. In this study we investigate the development of microbubble (MB) well array technology for sorting antigen-specific B-cells. Using Poisson statistics we delineate the important role that the fractional area of MB well opening and the cell seeding density have on determining cell seeding distribution in wells. The unique architecture of the MB well hinders captured cells from escaping the well and provides a unique microenvironmental niche that enables media changes as needed for extended cell culture. Using cell lines and primary B and T cells isolated from human peripheral blood we demonstrate the use of affinity capture agents coated in the MB wells to enrich for the selective capture of B cells. Important differences were noted in the efficacy of bovine serum albumin to block the nonspecific adsorption of primary cells relative to cell lines as well as the efficacy of the capture coatings using mixed primary B and T cells samples. These results emphasize the importance of using primary cells in technology development and suggest the need to utilize B cell capture agents that are insensitive to cell activation.

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
Fig. 6

Similar content being viewed by others

References

  • S. Agastin, U.B.T. Giang, Y. Geng, L.A. DeLouise, M.R. King, Continuously perfused microbubble array for 3D tumor spheroid model. Biomicrofluidics 5(2), 024110 (2011)

    Article  Google Scholar 

  • K. Bhadriraju, C.S. Chen, Engineering cellular microenvironments to improve cell-based drug testing. Drug Discov Today 7(11), 612–620 (2002)

    Article  Google Scholar 

  • G. Cassese, S. Arce, A.E. Hauser, K. Lehnert, B. Moewes, M. Mostarac, G. Muehlinghaus, M. Szyska, A. Radbruch, R.A. Manz, Plasma cell survival is mediated by synergistic effects of cytokines and adhesion-dependent signals. J Immunol 171, 1684–1690 (2003)

    Google Scholar 

  • S. Chandrasekaran, L.A. DeLouise, Enriching and characterizing cancer stem cell sub-populations in the WM115 melanoma cell line. Biomaterials 32(35), 9316–9327 (2011)

    Article  Google Scholar 

  • S. Chandrasekaran, U.B.T. Giang, M.R. King, L.A. DeLouise, Microenvironment induced spheroid to sheeting transition of immortalized human keratinocytes (HaCaT) cultured in microbubbles formed in polydimethylsiloxane. Biomaterials 32(29), 7159–7168 (2011)

    Article  Google Scholar 

  • M.C. Chevrier, I. Châteauneuf, M. Guérin, R. Lemieux, Sensitive detection of human IgG in ELISA using a monoclonal anti-IgG-peroxidase conjugate. Hybridoma Hybridom. 23(6), 362–367 (2004)

    Article  Google Scholar 

  • B. Coila. Blood Cells: Lymphocytes. Livestrong.com (2010)

  • J.E. Dick, Looking ahead in cancer stem cell research. Nat Biotechnol 27, 44–46 (2009)

    Article  Google Scholar 

  • K.R. Diener, S.N. Christo, S.S. Griesser, G.T. Sarvestani, K. Vasilev, H.J. Griesser, J.D. Hayball, Solid-state capture and real-time analysis of individual T cell activation via self-assembly of binding multimeric proteins on functionalized materials surfaces. Acta Biomater 8(1), 99–107 (2012)

    Article  Google Scholar 

  • J. El-Ali, P.K. Sorger, K.F. Jensen, Cells on chips. Nature 442(7101), 403–411 (2006)

    Article  Google Scholar 

  • E.L. Gelamo, M. Tabak, Spectroscopic studies on the interaction of bovine (BSA) and human (HSA) serum albumins with ionic surfactants, Spectrochim. Acta A 56, 2255–2271 (2000)

    Article  Google Scholar 

  • U.B.T. Giang, D. Lee, M.R. King, L.A. DeLouise, Microfabrication of cavities in polydimethylsiloxane using DRIE silicon molds. Lab Chip 7, 1660–1662 (2007)

    Article  Google Scholar 

  • U.B.T. Giang, M.R. King, L.A. DeLouise, Microfabrication of bubbular cavities in PDMS for cell sorting and microcell culture applications. J Bionic Eng 5(4), 308–316 (2008)

    Article  Google Scholar 

  • U.B.T. Giang, M. Jones, C.R. Virgile, J.M. Kaule, L.A. DeLouise. Characterization of PDMS gas expansion molding of microbubble arrays for cell culture applications. Biotechnol and Bioeng. Manuscript submitted. (2012)

  • Y. Gong, A.O. Ogunniyi, J.C. Love, Massively parallel detection of gene expression in single cells using subnanolitre wells. Lab Chip 10(18), 2334–2337 (2010)

    Article  Google Scholar 

  • Q. Han, E.M. Bradshaw, B. Nilsson, D.A. Hafler, J.C. Love, Multidimensional analysis of the frequencies and rates of cytokine secretion from single cells by quantitative microengraving. Lab Chip 10(11), 1391–1400 (2010)

    Article  Google Scholar 

  • A.D. Henn, M. Laski, H. Yang, S. Welle, X. Qiu, H. Miao, C.T. Barry, H. Wu, M.S. Zand, Functionally distinct subpopulations of CpG-Activated Memory B cells. Sci. Rep 2, 345 (2012). doi:10.1038/srep00345

    Article  Google Scholar 

  • P. Holmes, M. Al-Rubeai, Improved cell line development by a high throughput affinity capture surface display technique to select for high secretors. J Immunol Methods 230, 141–147 (1999)

    Article  Google Scholar 

  • A. Jin, T. Ozawa, K. Tajiri, T. Obata, S. Kondo, K. Kinoshita, S. Kadowaki, K. Takahashi, T. Sugiyama, H. Kishi, A. Muraguchi. A rapid and efficient single-cell manipulation method for screening antigen-specific antibody-secreting cells from human peripheral blood. Nat. Med. (2009)

  • M.R. King, L.T. Western, K. Rana, J.L. Liesveld, Biomolecular surfaces for the capture and reprogramming of circulating tumor cells. J Bionic Eng 6(4), 311–317 (2009)

    Article  Google Scholar 

  • I. Kurth, K. Franke, T. Pompe, M. Bornhauser, C. Werner, Hematopoietic stem and progenitor cells in adhesive microcavities. Integr Biol 1, 427–434 (2009)

    Article  Google Scholar 

  • S.Y. Kyu, J. Kobie, H. Yang, M.S. Zand, D.J. Topham, S.A. Quataert, I. Sanz, F.E. Lee, Frequencies of human influenza-specific antibody secreting cells or plasmablasts post vaccination from fresh and frozen peripheral blood mononuclear cells. J Immunol Methods 340(1), 42–47 (2009)

    Article  Google Scholar 

  • A. Lanzavecchia, Antigen-specific interaction between T and B cells. Nature 314, 537–539 (1985)

    Article  Google Scholar 

  • N. Li, A. Tourovskaia, A. Folch, Biology on a chip: microfabrication for studying the behavior of cultured cells. Crit Rev Biomed Eng 31(5–6), 423–488 (2003)

    Article  Google Scholar 

  • A.R. Liberskit, J.T. Delaney, U.S. Schubert, One Cell-One Well: a new approach to inkjet printing single cell microarrays. ACS Comb Sci 13(2), 190–195 (2011)

    Article  Google Scholar 

  • J.C. Love, J.L. Ronan, G.M. Grotenberg, A.G. van der Veen, H.L. Ploegh, A microengraving method for rapid selection of single cells producing antigen-specific antibodies. Nat Biotechnol 24(6), 703–707 (2006)

    Article  Google Scholar 

  • I. Meyvantsson, D.J. Beebe, Cell culture models in microfluidic systems. Annu Rev Anal Chem 1, 423–449 (2008)

    Article  Google Scholar 

  • M. Nikkah, J.S. Strobl, E.M. Schmelz, P.S. Roberts, H. Zhou, M. Agah, MCF10A and MDA-MB-231 human breast epithelial cell co-culture in silicon micro-arrays. Biomaterials 32, 7625–7632 (2011)

    Article  Google Scholar 

  • T.H. Park, M.L. Shuler, Integration of cell culture and microfabrication technology. Biotechnol Prog 19(2), 243–253 (2003)

    Article  Google Scholar 

  • J.R. Rettig, A. Folch, Large-scale single-cell trapping and imaging using microwell arrays. Anal Chem 77(17), 5628–5634 (2005)

    Article  Google Scholar 

  • D. Ryan, K. Ren, H. Wu, Single-cell assays. Biomicrofluidics 5(2), 021501 (2011)

    Article  Google Scholar 

  • D.J. Sherman, V.E. Kenanova, E.J. Lepin, K.E. McCabe, K. Kamei, M. Ohashi, S. Wang, H.R. Tseng, A.M. Wu, C.H. Behrenbruch, A differential cell capture assay for evaluating antibody interactions with cell surface targets. Anal Biochem 401(2), 173–181 (2010)

    Article  Google Scholar 

  • T.S. Soichi, Y. Kobayashi, Y. Takahata, F. Morimatsu, R. Shibata, T. Nishimura, Some human B and T cell epitopes of bovine serum albumin, the major beef allergen. Biochem Biophys Res Commun 293, 1348–1353 (2002)

    Article  Google Scholar 

  • Q. Song, Q. Han, E.M. Bradshaw, S.C. Kent, K. Raddassi, B. Nilsson, G.T. Nepom, D.A. Hafler, J.C. Love, On-chip activation and subsequent detection of individual antigen-specific T cells. Anal Chem 82(2), 473–477 (2010)

    Article  Google Scholar 

  • S.G. Tangye, E.K. Deenick, U. Palendira, C.S. Ma, T cell-B cell interactions in primary immunodeficiencies. Annals of the NY Acad Sci. 1250, 1–13 (2012)

    Article  Google Scholar 

  • S. Thorslund, R. Larsson, F. Nikolajeff, J. Bergquist, J. Sanchez, Bioactivated PDMS microchannel evaluated as sensor for human CD4+ cells- The concept of a point-of-care method for HIV monitoring. Sensor Actuat B- Chem 123(2), 847–855 (2007)

    Article  Google Scholar 

  • Y.C. Toh, K. Blagović, J. Voldman, Advancing stem cell research with microtechnologies: opportunities and challenges. Integr Biol 2(7–8), 305–325 (2010)

    Article  Google Scholar 

  • J. Voldman, M.L. Gray, M.A. Schmidt, Microfabrication in biology and medicine. Annu Rev Biomed Eng 1, 401–425 (1999)

    Article  Google Scholar 

  • H. Waldmann, Interactions between T and B cells: a review. J R Soc Med. 72(3), 198–202 (1979)

    MathSciNet  Google Scholar 

  • G.M. Walker, H.C. Zeringue, D.J. Beebe, Microenvironment design considerations for cellular scale studies. Lab Chip. 4(2), 91–97 (2004)

    Article  Google Scholar 

  • P.C. Weber, D.H. Ohlendorf, J.J. Wendoloski, F.R. Salemme, Structural origins of high-affinity biotin binding to streptavidin. Science 243(4887), 85–88 (1989)

    Article  Google Scholar 

  • I. Zaretsky, M. Polonsky, E. Shifrut, S. Reich-Zeliger, Y. Antebi, G. Aidelberg, N. Waysbort, N. Friedman, Monitoring the dynamics of primary T cell activation and differentiation using long term live cell imaging in microwell arrays. Lab Chip 12, 5007–5015 (2012)

    Article  Google Scholar 

Download references

Acknowledgements

This work was supported in part by the NSF CBET-0827862, the University of Rochester Developmental Center for AIDS Research grant P30AI078498 (NIH/NIAID), the University of Rochester Autoimmunity Center of Excellence U19AI056390 and by a UL1 TR000038 grant from the National Center for Advancing Translational Sciences, National Institutes of Health. The authors would like to thank Bo Zheng for the preparation of primary lymphocytes. The authors confirm that there are no known conflicts of interest associated with this publication.

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Lisa A. DeLouise.

Electronic supplementary material

Below is the link to the electronic supplementary material.

ESM 1

(PDF 487 kb)

Rights and permissions

Reprints and permissions

About this article

Cite this article

Jones, M.C., Kobie, J.J. & DeLouise, L.A. Characterization of cell seeding and specific capture of B cells in microbubble well arrays. Biomed Microdevices 15, 453–463 (2013). https://doi.org/10.1007/s10544-013-9745-0

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s10544-013-9745-0

Keywords

Navigation