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Screening of Antigen-Specific Antibody-Secreting Cells

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Abstract

High-throughput screening of antigen-specific antibody-secreting cells (ASC) is an essential step in the discovery of monoclonal antibodies (mAb) which are the key candidates for therapeutic agents. To produce specific mAbs, various procedures have been developed including phage display library construction, production of stable hybridoma, or Epstein-Barr virus-immortalized human ASCs. However, the selection of antigen-specific ASCs remains as the bottleneck of these already labor-intensive processes. The screening technology must be (1) highly specific to the target antigen, (2) sensitive for the detection of low-volume secretions from a single live cell, (3) nondestructive to allow further processing of the cells, and (4) high throughput. Conventionally, B cell ELISpot is widely used to identify ASCs due to its high sensitivity and selectivity. However, multiplexing and cell recovery are difficult to achieve. Recently, advances in microengraving and nanowell-based technologies enabled highly multiplexed single-cell secretion detections. Droplet platforms have also emerged as a promising tool to screen single ASCs in a high-throughput manner. In this chapter, these technologies will be discussed in terms of their merits and drawbacks, as well as their suitability in screening antigen-specific ASCs.

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References

  • Abali F, Broekmaat J, Tibbe A, Schasfoort RBM, Zeune L, Terstappen LWMM (2019) A microwell array platform to print and measure biomolecules produced by single cells. Lab Chip 19:1850–1859. https://doi.org/10.1039/C9LC00100J

    Article  Google Scholar 

  • Akselband Y, Moen PT Jr, McGrath P (2003) Isolation of rare isotype switch variants in hybridoma cell lines using an agarose gel microdrop-based protein secretion assay. Assay Drug Dev Technol 1:619–626

    Article  Google Scholar 

  • Almagro JC, Pedraza-Escalona M, Arrieta HI, Perez-Tapia SM (2019) Phage display libraries for antibody therapeutic discovery and development. Antibodies (Basel, Switzerland) 8. https://doi.org/10.3390/antib8030044

  • Barbas CF 3rd, Kang AS, Lerner RA, Benkovic SJ (1991) Assembly of combinatorial antibody libraries on phage surfaces: the gene III site. Proc Natl Acad Sci U S A 88:7978–7982. https://doi.org/10.1073/pnas.88.18.7978

    Article  Google Scholar 

  • Beerli RR, Rader C (2010) Mining human antibody repertoires. mAbs 2:365–378. Taylor & Francis, UK

    Google Scholar 

  • Behring EV (1890) Ãœber das zustandekommen der diphtherie-immunität und der tetanus-immunität bei thieren

    Google Scholar 

  • Bian H, Xu F, Jia Y, Wang L, Deng S, Jia A, Tang Y (2019) A new immunochromatographic assay for on-site detection of porcine epidemic diarrhea virus based on monoclonal antibodies prepared by using cell surface fluorescence immunosorbent assay. BMC Vet Res 15:32

    Article  Google Scholar 

  • Boonyaratanakornkit J, Taylor JJ (2019) Techniques to study antigen-specific B cell responses. Front Immunol 10:1694–1702

    Google Scholar 

  • Borth N, Zeyda M, Katinger H (2000) Efficient selection of high-producing subclones during gene amplification of recombinant Chinese hamster ovary cells by flow cytometry and cell sorting. Biotechnol Bioeng 71:266–273

    Article  Google Scholar 

  • Boyle MJ, Reiling L, Feng G, Langer C, Osier FH, Aspeling-Jones H, Cheng YS, Stubbs J, Tetteh KK, Conway DJ, McCarthy JS, Muller I, Marsh K, Anders RF, Beeson JG (2015) Human antibodies fix complement to inhibit Plasmodium falciparum invasion of erythrocytes and are associated with protection against malaria. Immunity 42:580–590. https://doi.org/10.1016/j.immuni.2015.02.012

    Article  Google Scholar 

  • Bradbury ARM, Trinklein ND, Thie H, Wilkinson IC, Tandon AK, Anderson S, Bladen CL, Jones B, Aldred SF, Bestagno M, Burrone O, Maynard J, Ferrara F, Trimmer JS, Gornemann J, Glanville J, Wolf P, Frenzel A, Wong J, Koh XY, Eng HY, Lane D, Lefranc MP, Clark M, Dubel S (2018) When monoclonal antibodies are not monospecific: hybridomas frequently express additional functional variable regions. mAbs 10:539–546. https://doi.org/10.1080/19420862.2018.1445456

    Article  Google Scholar 

  • Bradshaw EM, Kent SC, Tripuraneni V, Orban T, Ploegh HL, Hafler DA, Love JC (2008) Concurrent detection of secreted products from human lymphocytes by microengraving: cytokines and antigen-reactive antibodies. Clin Immunol 129:10–18. https://doi.org/10.1016/j.clim.2008.06.009

    Article  Google Scholar 

  • Brouzes E, Medkova M, Savenelli N, Marran D, Twardowski M, Hutchison JB, Rothberg JM, Link DR, Perrimon N, Samuels ML (2009) Droplet microfluidic technology for single-cell high-throughput screening. Proc Natl Acad Sci 106:14195–14200. https://doi.org/10.1073/pnas.0903542106

    Article  Google Scholar 

  • Carroll S, Al-Rubeai M (2004) The selection of high-producing cell lines using flow cytometry and cell sorting. Expert Opin Biol Ther 4:1821–1829

    Article  Google Scholar 

  • Carroll S, Al-Rubeai M (2005) ACSD labelling and magnetic cell separation: a rapid method of separating antibody secreting cells from non-secreting cells. J Immunol Methods 296:171–178

    Article  Google Scholar 

  • Chokkalingam V, Tel J, Wimmers F, Liu X, Semenov S, Thiele J, Figdor CG, Huck WT (2013) Probing cellular heterogeneity in cytokine-secreting immune cells using droplet- based microfluidics. Lab Chip 13:4740–4744

    Article  Google Scholar 

  • Collins DJ, Neild A, Demello A, Liu A-Q, Ai Y (2015) The Poisson distribution and beyond: methods for microfluidic droplet production and single cell encapsulation. Lab Chip 15:3439–3459. https://doi.org/10.1039/C5LC00614G

    Article  Google Scholar 

  • Corti D, Lanzavecchia A (2014) Efficient methods to isolate human monoclonal antibodies from memory B cells and plasma cells. Microbiol Spectr 2. https://doi.org/10.1128/microbiolspec.AID-0018-2014

  • Crowe JE Jr (2017) Principles of broad and potent antiviral human antibodies: insights for vaccine design. Cell Host Microbe 22:193–206. https://doi.org/10.1016/j.chom.2017.07.013

    Article  Google Scholar 

  • Debs BE, Utharala R, Balyasnikova IV, Griffiths AD, Merten CA (2012) Functional single-cell hybridoma screening using droplet-based microfluidics. Proc Natl Acad Sci 109:11570–11575. https://doi.org/10.1073/pnas.1204514109

    Article  Google Scholar 

  • Dekosky BJ, Ippolito GC, Deschner RP, Lavinder JJ, Wine Y, Rawlings BM, Varadarajan N, Giesecke C, Dörner T, Andrews SF, Wilson PC, Hunicke-Smith SP, Willson CG, Ellington AD, Georgiou G (2013) High-throughput sequencing of the paired human immunoglobulin heavy and light chain repertoire. Nat Biotechnol 31:166. https://doi.org/10.1038/nbt.2492. https://www.nature.com/articles/nbt.2492#supplementary-information

    Article  Google Scholar 

  • Dove A (1999) Drug screening—beyond the bottleneck. Nat Biotechnol 17:859–863. https://doi.org/10.1038/12845

    Article  Google Scholar 

  • Dura B, Liu Y, Voldman J (2014) Deformability-based microfluidic cell pairing and fusion. Lab Chip 14:2783–2790. https://doi.org/10.1039/c4lc00303a

    Article  Google Scholar 

  • Esfandiary L, Gupta N, Voigt A, Wanchoo A, Chan EKL, Sukumaran S, Nguyen CQ (2016) Single-cell antibody nanowells: a novel technology in detecting anti-SSA/Ro60- and anti-SSB/La autoantibody-producing cells in peripheral blood of rheumatic disease patients. Arthritis Res Ther 18:107–107. https://doi.org/10.1186/s13075-016-1010-5

    Article  Google Scholar 

  • Eyer K, Doineau RCL, Castrillon CE, Briseño-Roa L, Menrath V, Mottet G, England P, Godina A, Brient-Litzler E, Nizak C, Jensen A, Griffiths AD, Bibette J, Bruhns P, Baudry J (2017) Single-cell deep phenotyping of IgG-secreting cells for high- resolution immune monitoring. Nat Biotechnol 35:977. https://doi.org/10.1038/nbt.3964. https://www.nature.com/articles/nbt.3964#supplementary-information

    Article  Google Scholar 

  • Glukhova XA, Prusakova OV, Trizna JA, Zaripov MM, Afanas’eva GV, Glukhov AS, Poltavtseva RA, Ivanov AA, Avila-Rodriguez M, Barreto GE, Aliev G, Beletsky IP (2016) Updates on the production of therapeutic antibodies using human hybridoma technique. Curr Pharm Des 22:870–878

    Article  Google Scholar 

  • Graham BS, Ambrosino DM (2015) History of passive antibody administration for prevention and treatment of infectious diseases. Curr Opin HIV AIDS 10:129–134. https://doi.org/10.1097/coh.0000000000000154

    Article  Google Scholar 

  • Grilo AL, Mantalaris A (2018) The increasingly human and profitable monoclonal antibody market. Trends Biotechnol. https://doi.org/10.1016/j.tibtech.2018.05.014

  • Grilo AL, Mantalaris A (2019) The increasingly human and profitable monoclonal antibody market. Trends Biotechnol 37:9–16

    Article  Google Scholar 

  • Guo MT, Rotem A, Heyman JA, Weitz DA (2012) Droplet microfluidics for high-throughput biological assays. Lab Chip 12:2146–2155. https://doi.org/10.1039/C2LC21147E

    Article  Google Scholar 

  • Harlow E, Lane D (1988) A laboratory manual, vol 579. Cold Spring Harbor Laboratory, New York

    Google Scholar 

  • Hay M, Thomas DW, Craighead JL, Economides C, Rosenthal J (2014) Clinical development success rates for investigational drugs. Nat Biotechnol 32:40–51. https://doi.org/10.1038/nbt.2786

    Article  Google Scholar 

  • Hoet RM, Cohen EH, Kent RB, Rookey K, Schoonbroodt S, Hogan S, Rem L, Frans N, Daukandt M, Pieters H, Van Hegelsom R, Neer NC, Nastri HG, Rondon IJ, Leeds JA, Hufton SE, Huang L, Kashin I, Devlin M, Kuang G, Steukers M, Viswanathan M, Nixon AE, Sexton DJ, Hoogenboom HR, Ladner RC (2005) Generation of high-affinity human antibodies by combining donor-derived and synthetic complementarity-determining-region diversity. Nat Biotechnol 23:344–348. https://doi.org/10.1038/nbt1067

    Article  Google Scholar 

  • Huang L, Chen Y, Huang W, Wu H (2018) Cell pairing and polyethylene glycol (PEG)-mediated cell fusion using two-step centrifugation-assisted single-cell trapping (CAScT). Lab Chip 18:1113–1120. https://doi.org/10.1039/c7lc01131h

    Article  Google Scholar 

  • Itoh K, Reis AH, Hayhurst A, Sokol SY (2019) Isolation of nanobodies against Xenopus embryonic antigens using immune and non-immune phage display libraries. PLoS One 14:e0216083. https://doi.org/10.1371/journal.pone.0216083

    Article  Google Scholar 

  • Jin A, Ozawa T, Tajiri K, Obata T, Kondo S, Kinoshita K, Kadowaki S, Takahashi K, Sugiyama T, Kishi H, Muraguchi A (2009) A rapid and efficient single-cell manipulation method for screening antigen-specific antibody–secreting cells from human peripheral blood. Nat Med 15:1088. https://doi.org/10.1038/nm.1966. https://www.nature.com/articles/nm.1966#supplementary-information

    Article  Google Scholar 

  • Jin A, Ozawa T, Tajiri K, Obata T, Kishi H, Muraguchi A (2011) Rapid isolation of antigen-specific antibody-secreting cells using a chip-based immunospot array. Nat Protoc 6:668. https://doi.org/10.1038/nprot.2011.322

    Article  Google Scholar 

  • Keizer RJ, Huitema AD, Schellens JH, Beijnen JHJCP (2010) Clinical pharmacokinetics of therapeutic monoclonal antibodies. Clin Pharmacokinet 49:493–507

    Article  Google Scholar 

  • Kenney JS, Gray F, Ancel M-H, Dunne JF (1995) Production of monoclonal antibodies using a secretion capture report web. Bio/Technology 13:787

    Article  Google Scholar 

  • Kida A, Iijima M, Niimi T, Maturana ASD, Yoshimoto N, Kuroda SI (2013) Cell surface-fluorescence immunosorbent assay for real-time detection of hybridomas with efficient antibody secretion at the single-cell level. Anal Chem 85:1753–1759

    Article  Google Scholar 

  • Knappik A, Ge L, Honegger A, Pack P, Fischer M, Wellnhofer G, Hoess A, Wolle J, Pluckthun A, Virnekas B (2000) Fully synthetic human combinatorial antibody libraries (HuCAL) based on modular consensus frameworks and CDRs randomized with trinucleotides. J Mol Biol 296:57–86. https://doi.org/10.1006/jmbi.1999.3444

    Article  Google Scholar 

  • Knudsen C, Laustsen AH (2018) Recent advances in next generation snakebite antivenoms. Trop Med Infect Dis 3. https://doi.org/10.3390/tropicalmed3020042

  • Kohler G, Milstein C (1975) Continuous cultures of fused cells secreting antibody of predefined specificity. Nature 256:495–497. https://doi.org/10.1038/256495a0

    Article  Google Scholar 

  • Kugler J, Wilke S, Meier D, Tomszak F, Frenzel A, Schirrmann T, Dubel S, Garritsen H, Hock B, Toleikis L, Schutte M, Hust M (2015) Generation and analysis of the improved human HAL9/10 antibody phage display libraries. BMC Biotechnol 15:10. https://doi.org/10.1186/s12896-015-0125-0

    Article  Google Scholar 

  • Lecault V, Vaninsberghe M, Sekulovic S, Knapp DJHF, Wohrer S, Bowden W, Viel F, McLaughlin T, Jarandehei A, Miller M, Falconnet D, White AK, Kent DG, Copley MR, Taghipour F, Eaves CJ, Humphries RK, Piret JM, Hansen CL (2011) High-throughput analysis of single hematopoietic stem cell proliferation in microfluidic cell culture arrays. Nat Methods 8:581–586. https://doi.org/10.1038/nmeth.1614

    Article  Google Scholar 

  • Lewis GK, Ackerman ME, Scarlatti G, Moog C, Robert-Guroff M, Kent SJ, Overbaugh J, Reeves RK, Ferrari G, Thyagarajan B (2019) Knowns and unknowns of assaying antibody-dependent cell-mediated cytotoxicity against HIV-1. Front Immunol 10:1025. https://doi.org/10.3389/fimmu.2019.01025

    Article  Google Scholar 

  • Li X, Bian H, Yu S, Xiao W, Shen J, Lan C, Zhou K, Huang C, Wang L, Du D (2018) A rapid method for antigen-specific hybridoma clone isolation. Anal Chem 90:2224–2229

    Article  Google Scholar 

  • Love JC, Ronan JL, Grotenbreg GM, Van Der Veen AG, Ploegh HL (2006) A microengraving method for rapid selection of single cells producing antigen-specific antibodies. Nat Biotechnol 24:703–707. https://doi.org/10.1038/nbt1210

    Article  Google Scholar 

  • Lu LL, Suscovich TJ, Fortune SM, Alter G (2018) Beyond binding: antibody effector functions in infectious diseases. Nat Rev Immunol 18:46–61. https://doi.org/10.1038/nri.2017.106

    Article  Google Scholar 

  • Lynch RM, Tran L, Louder MK, Schmidt SD, Cohen M, Dersimonian R, Euler Z, Gray ES, Abdool Karim S, Kirchherr J, Montefiori DC, Sibeko S, Soderberg K, Tomaras G, Yang ZY, Nabel GJ, Schuitemaker H, Morris L, Haynes BF, Mascola JR (2012) The development of CD4 binding site antibodies during HIV-1 infection. J Virol 86:7588–7595. https://doi.org/10.1128/jvi.00734-12

    Article  Google Scholar 

  • Ma C, Fan R, Ahmad H, Shi Q, Comin-Anduix B, Chodon T, Koya RC, Liu C-C, Kwong GA, Radu CG, Ribas A, Heath JR (2011) A clinical microchip for evaluation of single immune cells reveals high functional heterogeneity in phenotypically similar T cells. Nat Med 17:738–743. https://doi.org/10.1038/nm.2375

    Article  Google Scholar 

  • Manz R, Assenmacher M, Pflüger E, Miltenyi S, Radbruch A (1995) Analysis and sorting of live cells according to secreted molecules, relocated to a cell-surface affinity matrix. Proc Natl Acad Sci 92:1921–1925

    Article  Google Scholar 

  • Mazutis L, Gilbert J, Ung WL, Weitz DA, Griffiths AD, Heyman JA (2013) Single-cell analysis and sorting using droplet-based microfluidics. Nat Protoc 8:870. https://doi.org/10.1038/nprot.2013.046. https://www.nature.com/articles/nprot.2013.046#supplementary-information

    Article  Google Scholar 

  • Mccafferty J, Griffiths AD, Winter G, Chiswell DJ (1990) Phage antibodies: filamentous phage displaying antibody variable domains. Nature 348:552–554. https://doi.org/10.1038/348552a0

    Article  Google Scholar 

  • Moreland NJ, Susanto P, Lim E, Tay MY, Rajamanonmani R, Hanson BJ, Vasudevan SG (2012) Phage display approaches for the isolation of monoclonal antibodies against dengue virus envelope domain III from human and mouse derived libraries. Int J Mol Sci 13:2618–2635. https://doi.org/10.3390/ijms13032618

    Article  Google Scholar 

  • Morris L, Chen X, Alam M, Tomaras G, Zhang R, Marshall DJ, Chen B, Parks R, Foulger A, Jaeger F, Donathan M, Bilska M, Gray ES, Abdool Karim SS, Kepler TB, Whitesides J, Montefiori D, Moody MA, Liao HX, Haynes BF (2011) Isolation of a human anti-HIV gp41 membrane proximal region neutralizing antibody by antigen-specific single B cell sorting. PLoS One 6:e23532. https://doi.org/10.1371/journal.pone.0023532

    Article  Google Scholar 

  • Nelson AL, Dhimolea E, Reichert JM (2010) Development trends for human monoclonal antibody therapeutics. Nat Rev Drug Discov 9:767

    Article  Google Scholar 

  • O’donnell EA, Ernst DN, Hingorani R (2013) Multiparameter flow cytometry: advances in high resolution analysis. Immune Netw 13:43–54

    Article  Google Scholar 

  • Ogunniyi AO, Story CM, Papa E, Guillen E, Love JC (2009) Screening individual hybridomas by microengraving to discover monoclonal antibodies. Nat Protoc 4:767. https://doi.org/10.1038/nprot.2009.40

    Article  Google Scholar 

  • Park S, Han J, Kim W, Lee GM, Kim H-S (2011) Rapid selection of single cells with high antibody production rates by microwell array. J Biotechnol 156:197–202. https://doi.org/10.1016/j.jbiotec.2011.08.031

    Article  Google Scholar 

  • Pinder CL, Kratochvil S, Cizmeci D, Muir L, Guo Y, Shattock RJ, McKay PF (2017) Isolation and characterization of antigen-specific plasmablasts using a novel flow cytometry–based Ig capture assay. J Immunol 199:4180–4188

    Article  Google Scholar 

  • Rorvig-Lund A, Bahadori A, Semsey S, Bendix PM, Oddershede LB (2015) Vesicle fusion triggered by optically heated gold nanoparticles. Nano Lett 15:4183–4188. https://doi.org/10.1021/acs.nanolett.5b01366

    Article  Google Scholar 

  • Ryman JT, Meibohm B (2017) Pharmacokinetics of monoclonal antibodies. CPT Pharmacometrics Syst Pharmacol 6:576–588. https://doi.org/10.1002/psp4.12224

    Article  Google Scholar 

  • Salazar G, Zhang N, Fu T-M, An Z (2017) Antibody therapies for the prevention and treatment of viral infections. NPJ Vaccines 2:19–19. https://doi.org/10.1038/s41541-017-0019-3

    Article  Google Scholar 

  • Scheid J, Mouquet H, Feldhahn N, Walker B, Pereyra F, Cutrell E, Seaman M, Mascola J, Wyatt R, Wardemann H, Nussenzweig MC (2009) A method for identification of HIV gp140 binding memory B cells in human blood. J Immunol Methods 343:65–67. https://doi.org/10.1016/j.jim.2008.11.012

    Article  Google Scholar 

  • Sen S, Hu W-S, Srienc F (1990) Flow cytometric study of hybridoma cell culture: correlation between cell surface fluorescence and IgG production rate. Enzym Microb Technol 12:571–576

    Article  Google Scholar 

  • Shembekar N, Hu H, Eustace D, Merten CA (2018) Single-cell droplet microfluidic screening for antibodies specifically binding to target cells. Cell Rep 22:2206–2215

    Article  Google Scholar 

  • Shimizu T, Kozono Y, Kozono H, Oda M, Azuma T (2004) Affinity maturation of secreted IgM pentamers on B cells. Int Immunol 16:675–684

    Article  Google Scholar 

  • Shuptrine CW, Surana R, Weiner LM (2012) Monoclonal antibodies for the treatment of cancer. Semin Cancer Biol 22:3–13. https://doi.org/10.1016/j.semcancer.2011.12.009

    Article  Google Scholar 

  • Singhal A, Haynes CA, Hansen CL (2010) Microfluidic measurement of antibody-antigen binding kinetics from low-abundance samples and single cells. Anal Chem 82:8671–8679. https://doi.org/10.1021/ac101956e

    Article  Google Scholar 

  • Slifka MK, Antia R, Whitmire JK, Ahmed R (1998) Humoral immunity due to long-lived plasma cells. Immunity 8:363–372. https://doi.org/10.1016/s1074-7613(00)80541-5

    Article  Google Scholar 

  • Smith SA, Crowe JE Jr (2015) Use of human hybridoma technology to isolate human monoclonal antibodies. Microbiol Spectr 3:Aid-0027-2014. https://doi.org/10.1128/microbiolspec.AID-0027-2014

    Article  Google Scholar 

  • Smith SA, De Alwis R, Kose N, Durbin AP, Whitehead SS, De Silva AM, Crowe JE Jr (2013) Human monoclonal antibodies derived from memory B cells following live attenuated dengue virus vaccination or natural infection exhibit similar characteristics. J Infect Dis 207:1898–1908. https://doi.org/10.1093/infdis/jit119

    Article  Google Scholar 

  • Tay MZ, Liu P, Williams LD, Mcraven MD, Sawant S, Gurley TC, Xu TT, Dennison SM, Liao HX, Chenine AL, Alam SM, Moody MA, Hope TJ, Haynes BF, Tomaras GD (2016) Antibody-mediated internalization of infectious HIV-1 Virions differs among antibody isotypes and subclasses. PLoS Pathog 12:e1005817. https://doi.org/10.1371/journal.ppat.1005817

    Article  Google Scholar 

  • Tay MZ, Wiehe K, Pollara J (2019) Antibody-dependent cellular phagocytosis in antiviral immune responses. Front Immunol 10:332. https://doi.org/10.3389/fimmu.2019.00332

    Article  Google Scholar 

  • Teh S-Y, Lin R, Hung L-H, Lee AP (2008) Droplet microfluidics. Lab Chip 8:198–220. https://doi.org/10.1039/B715524G

    Article  Google Scholar 

  • Tiller T, Meffre E, Yurasov S, Tsuiji M, Nussenzweig MC, Wardemann H (2008) Efficient generation of monoclonal antibodies from single human B cells by single cell RT-PCR and expression vector cloning. J Immunol Methods 329:112–124. https://doi.org/10.1016/j.jim.2007.09.017

    Article  Google Scholar 

  • Tokimitsu Y, Kishi H, Kondo S, Honda R, Tajiri K, Motoki K, Ozawa T, Kadowaki S, Obata T, Fujiki S, Tateno C, Takaishi H, Chayama K, Yoshizato K, Tamiya E, Sugiyama T, Muraguchi A (2007) Single lymphocyte analysis with a microwell array chip. Cytometry A 71A:1003–1010. https://doi.org/10.1002/cyto.a.20478

    Article  Google Scholar 

  • Walker LM, Phogat SK, Chan-Hui P-Y, Wagner D, Phung P, Goss JL, Wrin T, Simek MD, Fling S, Mitcham JL (2009) Broad and potent neutralizing antibodies from an African donor reveal a new HIV-1 vaccine target. Science 326:285–289

    Article  Google Scholar 

  • Wang J, Lu C (2006) Microfluidic cell fusion under continuous direct current voltage. Appl Phys Lett 89:234102

    Article  Google Scholar 

  • Ward AB, Wilson IA (2017) The HIV-1 envelope glycoprotein structure: nailing down a moving target. Immunol Rev 275:21–32. https://doi.org/10.1111/imr.12507

    Article  Google Scholar 

  • Weaver JC, Williams GB, Klibanov A, Demain AL (1988) Gel microdroplets: rapid detection and enumeration of individual microorganisms by their metabolic activity. Bio/Technology 6:1084

    Google Scholar 

  • Yamamura S, Kishi H, Tokimitsu Y, Kondo S, Honda R, Rao SR, Omori M, Tamiya E, Muraguchi A (2005) Single-cell microarray for analyzing cellular response. Anal Chem 77:8050–8056. https://doi.org/10.1021/ac0515632

    Article  Google Scholar 

  • Yu X, McGraw PA, House FS, Crowe JE Jr (2008) An optimized electrofusion-based protocol for generating virus-specific human monoclonal antibodies. J Immunol Methods 336:142–151. https://doi.org/10.1016/j.jim.2008.04.008

    Article  Google Scholar 

  • Zolot RS, Basu S, Million RP (2013) Antibody–drug conjugates. Nat Rev Drug Discov 12:259–260. https://doi.org/10.1038/nrd3980

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Hsu, M.N., Tay, Z.M., Lin, W.N., Wei, SC. (2020). Screening of Antigen-Specific Antibody-Secreting Cells. In: Santra, T., Tseng, FG. (eds) Handbook of Single Cell Technologies. Springer, Singapore. https://doi.org/10.1007/978-981-10-4857-9_27-1

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