Abstract
The immune system is a network of cells in which the constitutive members interact through dense and sometimes overlapping connections. The extreme complexity of this network poses a significant challenge for monitoring pathological conditions (e.g., food allergies, autoimmunity, and other chronic inflammatory diseases) and for discovering robust signatures of immunological responses that correlate with or predict the efficacy of interventions. The diversity among immune cells found in clinical samples (variations in cellular functions, lineages, and clonotypic breadth) requires approaches for monitoring immune responses with single-cell resolution.
In this chapter, we present an engineering approach for integrated single-cell analysis that uses interchangeable modular operations to provide a comprehensive characterization of the phenotypic, functional, and genetic variations for individual cells. We focus on the use of microfabricated devices to isolate and interrogate single cells, and on the analytical components that enable subsequent detection, correlation, and interpretation of multidimensional sets of data. We discuss specific challenges and opportunities in the realization of this concept, and review two examples where it has been implemented. The presented approach should provide a basis for the design and implementation of nonconventional bioanalytical processes for studying specific responses of an immune system.
This is a preview of subscription content, log in via an institution.
Buying options
Tax calculation will be finalised at checkout
Purchases are for personal use only
Learn about institutional subscriptionsReferences
Frankenstein, Z., Alon, U., and Cohen, I. R. (2006) The immune-body cytokine network defines a social architecture of cell interactions, Biol Direct 1, 32.
Fahey, J. L., Taylor, J. M. G., Detels, R., Hofmann, B., Melmed, R., Nishanian, P., and Giorgi, J. V. (1990) The Prognostic Value of Cellular and Serologic Markers in Infection with Human Immunodeficiency Virus Type-1, New Engl J Med 322, 166–172.
Shattock, R. J., Haynes, B. F., Pulendran, B., Flores, J., and Esparza, J. (2008) Improving defences at the portal of HIV entry: mucosal and innate immunity, PLoS Med 5, e81.
Spencer, S. L., Gaudet, S., Albeck, J. G., Burke, J. M., and Sorger, P. K. (2009) Non-genetic origins of cell-to-cell variability in TRAIL-induced apoptosis, Nature 459, 428-U144.
Jung, T., Schauer, U., Heusser, C., Neumann, C., and Rieger, C. (1993) Detection of intracellular cytokines by flow cytometry, J Immunol Methods 159, 197–207.
Czerkinsky, C. C., Nilsson, L. A., Nygren, H., Ouchterlony, O., and Tarkowski, A. (1983) A solid-phase enzyme-linked immunospot (ELISPOT) assay for enumeration of specific antibody-secreting cells, J Immunol Methods 65, 109–121.
Querec, T. D., Akondy, R. S., Lee, E. K., Cao, W., Nakaya, H. I., Teuwen, D., Pirani, A., Gernert, K., Deng, J., Marzolf, B., Kennedy, K., Wu, H., Bennouna, S., Oluoch, H., Miller, J., Vencio, R. Z., Mulligan, M., Aderem, A., Ahmed, R., and Pulendran, B. (2009) Systems biology approach predicts immunogenicity of the yellow fever vaccine in humans, Nat Immunol 10, 116–125.
Gaucher, D., Therrien, R., Kettaf, N., Angermann, B. R., Boucher, G., Filali-Mouhim, A., Moser, J. M., Mehta, R. S., Drake, D. R., Castro, E., Akondy, R., Rinfret, A., Yassine-Diab, B., Said, E. A., Chouikh, Y., Cameron, M. J., Clum, R., Kelvin, D., Somogyi, R., Greller, L. D., Balderas, R. S., Wilkinson, P., Pantaleo, G., Tartaglia, J., Haddad, E. K., and Sekaly, R. P. (2008) Yellow fever vaccine induces integrated multilineage and polyfunctional immune responses, J Exp Med 205, 3119–3131.
Arora, A., Simone, G., Salieb-Beugelaar, G. B., Kim, J. T., and Manz, A. (2010) Latest Developments in Micro Total Analysis Systems, Anal Chem 82, 4830–4847.
Chin, C. D., Linder, V., and Sia, S. K. (2007) Lab-on-a-chip devices for global health: Past studies and future opportunities, Lab Chip 7, 41–57.
Love, J. C. (2010) Integrated Process Design for Single-Cell Analytical Technologies, Aiche J 56, 2496–2502.
Fiorini, G. S., and Chiu, D. T. (2005) Disposable microfluidic devices: fabrication, function, and application, Biotechniques 38, 429–446.
Taylor, R. J., Falconnet, D., Niemisto, A., Ramsey, S. A., Prinz, S., Shmulevich, I., Galitski, T., and Hansen, C. L. (2009) Dynamic analysis of MAPK signaling using a high-throughput microfluidic single-cell imaging platform, P Natl Acad Sci USA 106, 3758–3763.
Thorsen, T., Maerkl, S. J., and Quake, S. R. (2002) Microfluidic large-scale integration, Science 298, 580–584.
Unger, M. A., Chou, H. P., Thorsen, T., Scherer, A., and Quake, S. R. (2000) Monolithic microfabricated valves and pumps by multilayer soft lithography, Science 288, 113–116.
Brouzes, E., Medkova, M., Savenelli, N., Marran, D., Twardowski, M., Hutchison, J. B., Rothberg, J. M., Link, D. R., Perrimon, N., and Samuels, M. L. (2009) Droplet microfluidic technology for single-cell high-throughput screening, P Natl Acad Sci USA 106, 14195–14200.
Clausell-Tormos, J., Lieber, D., Baret, J. C., El-Harrak, A., Miller, O. J., Frenz, L., Blouwolff, J., Humphry, K. J., Koster, S., Duan, H., Holtze, C., Weitz, D. A., Griffiths, A. D., and Merten, C. A. (2008) Droplet-based microfluidic platforms for the encapsulation and screening of mammalian cells and multicellular organisms (vol 15, pg 427, 2008), Chem Biol 15, 875–875.
Edd, J. F., Di Carlo, D., Humphry, K. J., Koster, S., Irimia, D., Weitz, D. A., and Toner, M. (2008) Controlled encapsulation of single-cells into monodisperse picolitre drops, Lab Chip 8, 1262–1264.
He, M. Y., Edgar, J. S., Jeffries, G. D. M., Lorenz, R. M., Shelby, J. P., and Chiu, D. T. (2005) Selective encapsulation of single cells and subcellular organelles into picoliter- and femtoliter-volume droplets, Anal Chem 77, 1539–1544.
Agresti, J. J., Antipov, E., Abate, A. R., Ahn, K., Rowat, A. C., Baret, J. C., Marquez, M., Klibanov, A. M., Griffiths, A. D., and Weitz, D. A. (2010) Ultrahigh-throughput screening in drop-based microfluidics for directed evolution, Proc Natl Acad Sci USA 107, 4004–4009.
Baret, J. C., Miller, O. J., Taly, V., Ryckelynck, M., El-Harrak, A., Frenz, L., Rick, C., Samuels, M. L., Hutchison, J. B., Agresti, J. J., Link, D. R., Weitz, D. A., and Griffiths, A. D. (2009) Fluorescence-activated droplet sorting (FADS): efficient microfluidic cell sorting based on enzymatic activity, Lab Chip 9, 1850–1858.
Di Carlo, D., Aghdam, N., and Lee, L. P. (2006) Single-cell enzyme concentrations, kinetics, and inhibition analysis using high-density hydrodynamic cell isolation arrays, Anal Chem 78, 4925–4930.
Skelley, A. M., Kirak, O., Suh, H., Jaenisch, R., and Voldman, J. (2009) Microfluidic control of cell pairing and fusion, Nature Methods 6, 147–152.
Love, J. C., Ronan, J. L., Grotenbreg, G. M., van der Veen, A. G., and Ploegh, H. L. (2006) A microengraving method for rapid selection of single cells producing antigen-specific antibodies, Nat Biotechnol 24, 703–707.
Rettig, J. R., and Folch, A. (2005) Large-scale single-cell trapping and imaging using microwell arrays, Anal Chem 77, 5628–5634.
Revzin, A., Sekine, K., Sin, A., Tompkins, R. G., and Toner, M. (2005) Development of a microfabricated cytometry platform for characterization and sorting of individual leukocytes, Lab Chip 5, 30–37.
Choi, J. H., Ogunniyi, A. O., Du, M. D., Du, M. N., Kretschmann, M., Eberhardt, J., and Love, J. C. (2010) Development and Optimization of a Process for Automated Recovery of Single Cells Identified by Microengraving, Biotechnol Progr 26, 888–895.
Jin, A., Ozawa, T., Tajiri, K., Obata, T., Kondo, S., Kinoshita, K., Kadowaki, S., Takahashi, K., Sugiyama, T., Kishi, H., and Muraguchi, A. (2009) A rapid and efficient single-cell manipulation method for screening antigen-specific antibody-secreting cells from human peripheral blood, Nature Medicine 15, 1088-U1146.
Di Carlo, D., and Lee, L. P. (2006) Dynamic single-cell analysis for quantitative biology, Anal Chem 78, 7918–7925.
Park, J. Y., Morgan, M., Sachs, A. N., Samorezov, J., Teller, R., Shen, Y., Pienta, K. J., and Takayama, S. (2010) Single cell trapping in larger microwells capable of supporting cell spreading and proliferation, Microfluid Nanofluid 8, 263–268.
Lee, W. C., Rigante, S., Pisano, A. P., and Kuypers, F. A. (2010) Large-scale arrays of picolitre chambers for single-cell analysis of large cell populations, Lab Chip 10, 2952–2958.
Park, M. C., Hur, J. Y., Cho, H. S., Park, S. H., and Suh, K. Y. (2011) High-throughput single-cell quantification using simple microwell-based cell docking and programmable time-course live-cell imaging, Lab Chip 11, 79–86.
Eriksson, E., Sott, K., Lundqvist, F., Sveningsson, M., Scrimgeour, J., Hanstorp, D., Goksor, M., and Graneli, A. (2010) A microfluidic device for reversible environmental changes around single cells using optical tweezers for cell selection and positioning, Lab Chip 10, 617–625.
Lu, Z., Moraes, C., Ye, G., Simmons, C. A., and Sun, Y. (2010) Single Cell Deposition and Patterning with a Robotic System, PLoS One 5, -.
Zola, H., Swart, B., Banham, A., Barry, S., Beare, A., Bensussan, A., Boumsell, L., Buckley, C. D., Buhring, H. J., Clark, G., Engel, P., Fox, D., Jin, B. Q., Macardle, P. J., Malavasi, F., Mason, D., Stockinger, H., and Yang, X. F. (2007) CD molecules 2006 - Human cell differentiation molecules, J Immunol Methods 319, 1–5.
Perfetto, S. P., Chattopadhyay, P. K., and Roederer, M. (2004) Innovation - Seventeen-colour flow cytometry: unravelling the immune system, Nat Rev Immunol 4, 648-U645.
Sitton, G., and Srienc, F. (2009) Flow Cytometry Without Alignment of Collection Optics, Cytom Part A 75A, 990–998.
Song, Q., Han, Q., Bradshaw, E. M., Kent, S. C., Raddassi, K., Nilsson, B., Nepom, G. T., Hafler, D. A., and Love, J. C. (2010) On-Chip Activation and Subsequent Detection of Individual Antigen-Specific T Cells, Anal Chem 82, 473–477.
Harnett, M. M. (2007) Laser scanning cytometry: understanding the immune system in situ, Nat Rev Immunol 7, 897–904.
Ogunniyi, A. O., Story, C. M., Papa, E., Guillen, E., and Love, J. C. (2009) Screening individual hybridomas by microengraving to discover monoclonal antibodies, Nat Protoc 4, 767–782.
Bandura, D. R., Baranov, V. I., Ornatsky, O. I., Antonov, A., Kinach, R., Lou, X. D., Pavlov, S., Vorobiev, S., Dick, J. E., and Tanner, S. D. (2009) Mass Cytometry: Technique for Real Time Single Cell Multitarget Immunoassay Based on Inductively Coupled Plasma Time-of-Flight Mass Spectrometry, Anal Chem 81, 6813–6822.
Tanner, S. D., Bandura, D. R., Ornatsky, O., Baranov, V. I., Nitz, M., and Winnik, M. A. (2008) Flow cytometer with mass spectrometer detection for massively multiplexed single-cell biomarker assay, Pure Appl Chem 80, 2627–2641.
Jung, T., Schauer, U., Heusser, C., Neumann, C., and Rieger, C. (1993) Detection of Intracellular Cytokines by Flow-Cytometry, J Immunol Methods 159, 197–207.
Sachs, K., Perez, O., Pe’er, D., Lauffenburger, D. A., and Nolan, G. P. (2005) Causal protein-signaling networks derived from multiparameter single-cell data, Science 308, 523–529.
Assenmacher, M., Lohning, M., and Radbruch, A. (2002) Detection and isolation of cytokine secreting cells using the cytometric cytokine secretion assay, Curr Protoc Immunol Chapter 6, Unit 6 27.
Streeck, H., Frahm, N., and Walker, B. D. (2009) The role of IFN-gamma Elispot assay in HIV vaccine research, Nat Protoc 4, 461–469.
Zhu, H., Stybayeva, G., Silangcruz, J., Yan, J., Ramanculov, E., Dandekar, S., George, M. D., and Revzin, A. (2009) Detecting Cytokine Release from Single T-cells, Anal Chem 81, 8150–8156.
Han, Q., Bradshaw, E. M., Nilsson, B., Hafler, D. A., and Love, J. C. (2010) Multidimensional analysis of the frequencies and rates of cytokine secretion from single cells by quantitative microengraving, Lab Chip 10, 1391–1400.
Story, C. M., Papa, E., Hu, C. C. A., Ronan, J. L., Herlihy, K., Ploegh, H. L., and Love, J. C. (2008) Profiling antibody responses by multiparametric analysis of primary B cells, P Natl Acad Sci USA 105, 17902–17907.
Love, K. R., Panagiotou, V., Jiang, B., Stadheim, T. A., and Love, J. C. (2010) Integrated single-cell analysis shows Pichia pastoris secretes protein stochastically, Biotechnol Bioeng 106, 319–325.
Nagorsen, D., Marincola, F. M., Hodgkin, P., Hawkins, E., Hasbold, J., Gett, A., Deenick, E., Todd, H., and Hommel, M. (2005) Monitoring T Cell Proliferation, In Analyzing T Cell Responses, pp 123–141, Springer Netherlands.
Rothaeusler, K., and Baumgarth, N. (2007) Assessment of cell proliferation by 5-bromodeoxyuridine (BrdU) labeling for multicolor flow cytometry, Curr Protoc Cytom Chapter 7, 7.31.31-37.31.31.
Yu, Y., Arora, A., Min, W., Roifman, C. M., and Grunebaum, E. (2009) EdU incorporation is an alternative non-radioactive assay to ((3)H)thymidine uptake for in vitro measurement of mice T-cell proliferations, J Immunol Methods 350, 29–35.
Quah, B. J., Warren, H. S., and Parish, C. R. (2007) Monitoring lymphocyte proliferation in vitro and in vivo with the intracellular fluorescent dye carboxyfluorescein diacetate succinimidyl ester, Nat Protoc 2, 2049–2056.
Hawkins, E. D., Markham, J. F., McGuinness, L. P., and Hodgkin, P. D. (2009) A single-cell pedigree analysis of alternative stochastic lymphocyte fates, Proc Natl Acad Sci USA 106, 13457–13462.
Albrecht, D. R., Underhill, G. H., Resnikoff, J., Mendelson, A., Bhatia, S. N., and Shah, J. V. (2010) Microfluidics-integrated time-lapse imaging for analysis of cellular dynamics, Integr Biol (Camb) 2, 278–287.
Rowat, A. C., Bird, J. C., Agresti, J. J., Rando, O. J., and Weitz, D. A. (2009) Tracking lineages of single cells in lines using a microfluidic device, P Natl Acad Sci USA 106, 18149–18154.
Russell, J. H., and Ley, T. J. (2002) Lymphocyte-mediated cytotoxicity, Annu Rev Immunol 20, 323–370.
Aubry, J. P., Blaecke, A., Lecoanet-Henchoz, S., Jeannin, P., Herbault, N., Caron, G., Moine, V., and Bonnefoy, J. Y. (1999) Annexin V used for measuring apoptosis in the early events of cellular cytotoxicity, Cytometry 37, 197–204.
Kim, G. G., Donnenberg, V. S., Donnenberg, A. D., mGooding, W., and Whiteside, T. L. (2007) A novel multiparametric flow cytometry-based cytotoxicity assay simultaneously immunophenotypes effector cells: comparisons to a 4 h 51Cr-release assay, J Immunol Methods 325, 51–66.
Wlodkowic, D., Skommer, J., McGuinness, D., Faley, S., Kolch, W., Darzynkiewicz, Z., and Cooper, J. M. (2009) Chip-based dynamic real-time quantification of drug-induced cytotoxicity in human tumor cells, Anal Chem 81, 6952–6959.
Liu, L., Chahroudi, A., Silvestri, G., Wernett, M. E., Kaiser, W. J., Safrit, J. T., Komoriya, A., Altman, J. D., Packard, B. Z., and Feinberg, M. B. (2002) Visualization and quantification of T cell-mediated cytotoxicity using cell-permeable fluorogenic caspase substrates, Nat Med 8, 185–189.
Packard, B. Z., Telford, W. G., Komoriya, A., and Henkart, P. A. (2007) Granzyme B activity in target cells detects attack by cytotoxic lymphocytes, J Immunol 179, 3812–3820.
Alter, G., Malenfant, J. M., and Altfeld, M. (2004) CD107a as a functional marker for the identification of natural killer cell activity, J Immunol Methods 294, 15–22.
Betts, M. R., Brenchley, J. M., Price, D. A., De Rosa, S. C., Douek, D. C., Roederer, M., and Koup, R. A. (2003) Sensitive and viable identification of antigen-specific CD8+ T cells by a flow cytometric assay for degranulation, J Immunol Methods 281, 65–78.
Hersperger, A. R., Makedonas, G., and Betts, M. R. (2008) Flow cytometric detection of perforin upregulation in human CD8 T cells, Cytometry A 73, 1050–1057.
Zuber, B., Levitsky, V., Jonsson, G., Paulie, S., Samarina, A., Grundstrom, S., Metkar, S., Norell, H., Callender, G. G., Froelich, C., and Ahlborg, N. (2005) Detection of human perforin by ELISpot and ELISA: ex vivo identification of virus-specific cells, J Immunol Methods 302, 13–25.
Shafer-Weaver, K., Sayers, T., Strobl, S., Derby, E., Ulderich, T., Baseler, M., and Malyguine, A. (2003) The Granzyme B ELISPOT assay: an alternative to the 51Cr-release assay for monitoring cell-mediated cytotoxicity, J Transl Med 1, 14.
Bhat, R., and Watzl, C. (2007) Serial killing of tumor cells by human natural killer cells–enhancement by therapeutic antibodies, PLoS One 2, e326.
Jenkins, M. R., La Gruta, N. L., Doherty, P. C., Trapani, J. A., Turner, S. J., and Waterhouse, N. J. (2009) Visualizing CTL activity for different CD8+ effector T cells supports the idea that lower TCR/epitope avidity may be advantageous for target cell killing, Cell Death Differ 16, 537–542.
Faley, S., Seale, K., Hughey, J., Schaffer, D. K., VanCompernolle, S., McKinney, B., Baudenbacher, F., Unutmaz, D., and Wikswo, J. P. (2008) Microfluidic platform for real-time signaling analysis of multiple single T cells in parallel, Lab Chip 8, 1700–1712.
Guldevall, K., Vanherberghen, B., Frisk, T., Hurtig, J., Christakou, A. E., Manneberg, O., Lindstrom, S., Andersson-Svahn, H., Wiklund, M., and Onfelt, B. (2010) Imaging immune surveillance of individual natural killer cells confined in microwell arrays, PLoS One 5, e15453.
Snyder, J. E., Bowers, W. J., Livingstone, A. M., Lee, F. E., Federoff, H. J., and Mosmann, T. R. (2003) Measuring the frequency of mouse and human cytotoxic T cells by the Lysispot assay: independent regulation of cytokine secretion and short-term killing, Nat Med 9, 231–235.
Elowitz, M. B., Levine, A. J., Siggia, E. D., and Swain, P. S. (2002) Stochastic gene expression in a single cell, Science 297, 1183–1186.
Stahlberg, A., and Bengtsson, M. (2010) Single-cell gene expression profiling using reverse transcription quantitative real-time PCR, Methods 50, 282–288.
Marcus, J. S., Anderson, W. F., and Quake, S. R. (2006) Microfluidic single-cell mRNA isolation and analysis, Anal Chem 78, 3084–3089.
Gong, Y. A., Ogunniyi, A. O., and Love, J. C. (2010) Massively parallel detection of gene expression in single cells using subnanolitre wells, Lab Chip 10, 2334–2337.
Nakano, M., Nakai, N., Kurita, H., Komatsu, J., Takashima, K., Katsura, S., and Mizuno, A. (2005) Single-molecule reverse transcription polymerase chain reaction using water-in-oil emulsion, J Biosci Bioeng 99, 293–295.
Mardis, E. R. (2008) The impact of next-generation sequencing technology on genetics, Trends Genet 24, 133–141.
Petrovsky, N., and Harrison, L. C. (1995) Cytokine-based human whole blood assay for the detection of antigen-reactive T cells, J Immunol Methods 186, 37–46.
Helms, T., Boehm, B. O., Asaad, R. J., Trezza, R. P., Lehmann, P. V., and Tary-Lehmann, M. (2000) Direct visualization of cytokine-producing recall antigen-specific CD4 memory T cells in healthy individuals and HIV patients, J Immunol 164, 3723–3732.
Guerkov, R. E., Targoni, O. S., Kreher, C. R., Boehm, B. O., Herrera, M. T., Tary-Lehmann, M., Lehmann, P. V., and Schwander, S. K. (2003) Detection of low-frequency antigen-specific IL-10-producing CD4(+) T cells via ELISPOT in PBMC: cognate vs. nonspecific production of the cytokine, J Immunol Methods 279, 111–121.
Zeng, Y., Novak, R., Shuga, J., Smith, M. T., and Mathies, R. A. (2010) High-performance single cell genetic analysis using microfluidic emulsion generator arrays, Anal Chem 82, 3183–3190.
Mlecnik, B., Sanchez-Cabo, F., Charoentong, P., Bindea, G., Pages, F., Berger, A., Galon, J., and Trajanoski, Z. (2010) Data integration and exploration for the identification of molecular mechanisms in tumor-immune cells interaction, BMC Genomics 11 Suppl 1, S7.
Gevaert, O., De Smet, F., Timmerman, D., Moreau, Y., and De Moor, B. (2006) Predicting the prognosis of breast cancer by integrating clinical and microarray data with Bayesian networks, Bioinformatics 22, e184–190.
Huang, S. S., and Fraenkel, E. (2009) Integrating proteomic, transcriptional, and interactome data reveals hidden components of signaling and regulatory networks, Sci Signal 2, ra40.
Genser, B., Cooper, P. J., Yazdanbakhsh, M., Barreto, M. L., and Rodrigues, L. C. (2007) A guide to modern statistical analysis of immunological data, BMC Immunol 8, 27.
Alizadeh, A. A., Eisen, M. B., Davis, R. E., Ma, C., Lossos, I. S., Rosenwald, A., Boldrick, J. C., Sabet, H., Tran, T., Yu, X., Powell, J. I., Yang, L., Marti, G. E., Moore, T., Hudson, J., Jr., Lu, L., Lewis, D. B., Tibshirani, R., Sherlock, G., Chan, W. C., Greiner, T. C., Weisenburger, D. D., Armitage, J. O., Warnke, R., Levy, R., Wilson, W., Grever, M. R., Byrd, J. C., Botstein, D., Brown, P. O., and Staudt, L. M. (2000) Distinct types of diffuse large B-cell lymphoma identified by gene expression profiling, Nature 403, 503–511.
Berry, M. P., Graham, C. M., McNab, F. W., Xu, Z., Bloch, S. A., Oni, T., Wilkinson, K. A., Banchereau, R., Skinner, J., Wilkinson, R. J., Quinn, C., Blankenship, D., Dhawan, R., Cush, J. J., Mejias, A., Ramilo, O., Kon, O. M., Pascual, V., Banchereau, J., Chaussabel, D., and O’Garra, A. (2010) An interferon-inducible neutrophil-driven blood transcriptional signature in human tuberculosis, Nature 466, 973–977.
Loo, L. H., Wu, L. F., and Altschuler, S. J. (2007) Image-based multivariate profiling of drug responses from single cells, Nat Methods 4, 445–453.
Author information
Authors and Affiliations
Corresponding author
Editor information
Editors and Affiliations
Rights and permissions
Copyright information
© 2012 Springer Science+Business Media, LLC
About this protocol
Cite this protocol
Yalçın, A., Yamanaka, Y.J., Love, J.C. (2012). Analytical Technologies for Integrated Single-Cell Analysis of Human Immune Responses. In: Lindström, S., Andersson-Svahn, H. (eds) Single-Cell Analysis. Methods in Molecular Biology, vol 853. Humana Press. https://doi.org/10.1007/978-1-61779-567-1_16
Download citation
DOI: https://doi.org/10.1007/978-1-61779-567-1_16
Published:
Publisher Name: Humana Press
Print ISBN: 978-1-61779-566-4
Online ISBN: 978-1-61779-567-1
eBook Packages: Springer Protocols