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Progress in the development of immunoanalytical methods incorporating recombinant antibodies to small molecular weight biotoxins

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Abstract

Rapid immunoanalytical screening of food and environmental samples for small molecular weight (hapten) biotoxin contaminations requires the production of antibody reagents that possess the requisite sensitivity and specificity. To date animal-derived polyclonal (pAb) and monoclonal (mAb) antibodies have provided the binding element of the majority of these assays but recombinant antibodies (rAb) isolated from in vitro combinatorial phage display libraries are an exciting alternative due to (1) circumventing the need for experimental animals, (2) speed of production in commonly used in vitro expression systems and (3) subsequent molecular enhancement of binder performance. Short chain variable fragments (scFv) have been the most commonly employed rAb reagents for hapten biotoxin detection over the last two decades but antibody binding fragments (Fab) and single domain antibodies (sdAb) are increasing in popularity due to increased expression efficiency of functional binders and superior resistance to solvents. rAb-based immunochromatographic assays and surface plasmon resonance (SPR) biosensors have been reported to detect sub-regulatory levels of fungal (mycotoxins), marine (phycotoxins) and aquatic biotoxins in a wide range of food and environmental matrices, however this technology has yet to surpass the performances of the equivalent mAb- and pAb-based formats. As such the full potential of rAb technology in hapten biotoxin detection has yet to be achieved, but in time the inherent advantages of engineered rAb are set to provide the next generation of ultra-high performing binder reagents for the rapid and specific detection of hapten biotoxins.

Schematic representation of (A) affinity selection of phage-displayed recombinant antibody (rAb) and (B) immunoglobulin antibody structures and the corresponding antibody fragments

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References

  1. Van Egmond HP (2004) Natural toxins: risks, regulations and the analytical situation in Europe. Anal Bioanal Chem 378:1152–1160. doi:10.1007/s00216-003-2373-4

    Google Scholar 

  2. Hess P (2010) Requirements for screening and confirmatory methods for the detection and quantification of marine biotoxins in end-product and official control. Anal Bioanal Chem 397:1683–1694. doi:10.1007/s00216-009-3444-y

    CAS  Google Scholar 

  3. Di Stefano V, Avellone G, Bongiorno D et al (2012) Applications of liquid chromatography-mass spectrometry for food analysis. J Chromatogr A 1259:74–85. doi:10.1016/j.chroma.2012.04.023

    Google Scholar 

  4. Campbell K, Vilariño N, Botana LM, Elliott CT (2011) A European perspective on progress in moving away from the mouse bioassay for marine-toxin analysis. TrAC Trends Anal Chem 30:239–253. doi:10.1016/j.trac.2010.10.010

    CAS  Google Scholar 

  5. Sheedy C, MacKenzie CR, Hall JC (2007) Isolation and affinity maturation of hapten-specific antibodies. Biotechnol Adv 25:333–352. doi:10.1016/j.biotechadv.2007.02.003

    CAS  Google Scholar 

  6. Yau KYF, Lee H, Hall JC (2003) Emerging trends in the synthesis and improvement of hapten-specific recombinant antibodies. Biotechnol Adv 21:599–637

    CAS  Google Scholar 

  7. Fodey T, Leonard P, O’Mahony J et al (2011) Developments in the production of biological and synthetic binders for immunoassay and sensor-based detection of small molecules. TrAC Trends Anal Chem 30:254–269. doi:10.1016/j.trac.2010.10.011

    CAS  Google Scholar 

  8. Nishimiya D (2014) Proteins improving recombinant antibody production in mammalian cells. Appl Microbiol Biotechnol 98:1031–1042. doi:10.1007/s00253-013-5427-3

    CAS  Google Scholar 

  9. Web of Science. http://apps.webofknowledge.com/Search.do?product=UA&SID=N2JYPErxqToSQuxv2DD&search_mode=GeneralSearch&prID=f7835cc2-b4b4-45e0-882d-f9d16c41d8df

  10. Smith GP (1985) Filamentous fusion phage: novel expression vectors that display cloned antigens on the virion surface. Science 228:1315–1317

    CAS  Google Scholar 

  11. Hoogenboom HR (2002) Overview of antibody phage-display technology and its applications. Methods Mol Biol 178:1–37

    CAS  Google Scholar 

  12. Holliger P, Hudson PJ (2005) Engineered antibody fragments and the rise of single domains. Nat Biotechnol 23:1126–1136. doi:10.1038/nbt1142

    CAS  Google Scholar 

  13. Miersch S, Sidhu SS (2012) Synthetic antibodies: concepts, potential and practical considerations. Methods 57:486–498. doi:10.1016/j.ymeth.2012.06.012

    CAS  Google Scholar 

  14. Xu JL, Davis MM (2000) Diversity in the CDR3 region of V(H) is sufficient for most antibody specificities. Immunity 13:37–45

    CAS  Google Scholar 

  15. Wall JG, Plückthun A (1995) Effects of overexpressing folding modulators on the in vivo folding of heterologous proteins in Escherichia coli. Curr Opin Biotechnol 6:507–516

    CAS  Google Scholar 

  16. Muyldermans S (2013) Nanobodies: natural single-domain antibodies. Annu Rev Biochem 82:775–797. doi:10.1146/annurev-biochem-063011-092449

    CAS  Google Scholar 

  17. De Marco A (2011) Biotechnological applications of recombinant single-domain antibody fragments. Microb Cell Fact 10:44. doi:10.1186/1475-2859-10-44

    Google Scholar 

  18. Vincke C, Muyldermans S (2012) Single Domain Antibodies. In: Saerens D (ed) Muyldermans S (eds)Humana Press. Totowa, NJ, pp 15–26

    Google Scholar 

  19. Alvarez-Rueda N, Behar G, Ferré V et al (2007) Generation of llama single-domain antibodies against methotrexate, a prototypical hapten. Mol Immunol 44:1680–1690. doi:10.1016/j.molimm.2006.08.007

    CAS  Google Scholar 

  20. Harmsen MM, De Haard HJ (2007) Properties, production, and applications of camelid single-domain antibody fragments. Appl Microbiol Biotechnol 77:13–22. doi:10.1007/s00253-007-1142-2

    CAS  Google Scholar 

  21. Muyldermans S, Cambillau C, Wyns L (2001) Recognition of antigens by single- domain antibody fragments : the superfluous luxury of paired domains. 26:230–235

  22. Spinelli S, Tegoni M, Frenken L et al (2001) Lateral recognition of a dye hapten by a llama VHH domain. J Mol Biol 311:123–129. doi:10.1006/jmbi.2001.4856

    CAS  Google Scholar 

  23. Sheedy C, Yau KYF, Hirama T et al (2006) Selection, characterization, and CDR shuffling of naive llama single-domain antibodies selected against auxin and their cross-reactivity with auxinic herbicides from four chemical families. J Agric Food Chem 54:3668–3678

    CAS  Google Scholar 

  24. Kobayashi N, Oyama H (2011) Antibody engineering toward high-sensitivity high-throughput immunosensing of small molecules. Analyst 136:642–651. doi:10.1039/c0an00603c

    CAS  Google Scholar 

  25. Ponsel D, Neugebauer J, Ladetzki-Baehs K, Tissot K (2011) High affinity, developability and functional size: the holy grail of combinatorial antibody library generation. Molecules 16:3675–3700. doi:10.3390/molecules16053675

    CAS  Google Scholar 

  26. Boder ET, Midelfort KS, Wittrup KD (2000) Directed evolution of antibody fragments with monovalent femtomolar antigen-binding affinity. Proc Natl Acad Sci U S A 97:10701–10705. doi:10.1073/pnas.170297297

    CAS  Google Scholar 

  27. Ueda H (2002) Open sandwich immunoassay: a novel immunoassay approach based on the interchain interaction of an antibody variable region. J Biosci Bioeng 94:614–619

    CAS  Google Scholar 

  28. Sherwood LJ, Hayhurst A (2012) Hapten mediated display and pairing of recombinant antibodies accelerates assay assembly for biothreat countermeasures. Sci Rep 2:807. doi:10.1038/srep00807

    Google Scholar 

  29. Zhang J, Tanha J, Hirama T et al (2004) Pentamerization of single-domain antibodies from phage libraries: a novel strategy for the rapid generation of high-avidity antibody reagents. J Mol Biol 335:49–56

    CAS  Google Scholar 

  30. Stone E, Hirama T, Tanha J et al (2007) The assembly of single domain antibodies into bispecific decavalent molecules. J Immunol Methods 318:88–94. doi:10.1016/j.jim.2006.10.006

    CAS  Google Scholar 

  31. Hoogenboom HR, Griffiths AD, Johnson KS et al (1991) Multi-subunit proteins on the surface of filamentous phage: methodologies for displaying antibody (Fab) heavy and light chains. Nucleic Acids Res 19:4133–4137

    CAS  Google Scholar 

  32. Perelson AS, Oster GF (1979) Theoretical studies of clonal selection: minimal antibody repertoire size and reliability of self-non-self discrimination. J Theor Biol 81:645–670

    CAS  Google Scholar 

  33. Mix E, Goertsches R, Zett UK (2006) Immunoglobulins--basic considerations. J Neurol 253(Suppl):V9–V17. doi:10.1007/s00415-006-5002-2

    Google Scholar 

  34. Griffiths AD, Williams SC, Hartley O et al (1994) Isolation of high affinity human antibodies directly from large synthetic repertoires. EMBO J 13:3245–3260

    CAS  Google Scholar 

  35. MacCallum RM, Martin AC, Thornton JM (1996) Antibody-antigen interactions: contact analysis and binding site topography. J Mol Biol 262:732–745. doi:10.1006/jmbi.1996.0548

    CAS  Google Scholar 

  36. Persson H, Lantto J, Ohlin M (2006) A focused antibody library for improved hapten recognition. J Mol Biol 357:607–620. doi:10.1016/j.jmb.2006.01.004

    CAS  Google Scholar 

  37. Braunagel M, Little M (1997) Construction of a semisynthetic antibody library using trinucleotide oligos. Nucleic Acids Res 25:4690–4691

    CAS  Google Scholar 

  38. Marks JD, Hoogenboom HR, Bonnert TP et al (1991) By-passing immunization. Human antibodies from V-gene libraries displayed on phage. J Mol Biol 222:581–597

    CAS  Google Scholar 

  39. Vaughan TJ, Williams AJ, Pritchard K et al (1996) Human antibodies with sub-nanomolar affinities isolated from a large non-immunized phage display library. Nat Biotechnol 14:309–314. doi:10.1038/nbt0396-309

    CAS  Google Scholar 

  40. Pansri P, Jaruseranee N, Rangnoi K et al (2009) A compact phage display human scFv library for selection of antibodies to a wide variety of antigens. BMC Biotechnol 9:6. doi:10.1186/1472-6750-9-6

    Google Scholar 

  41. De Wildt RM, Mundy CR, Gorick BD, Tomlinson IM (2000) Antibody arrays for high-throughput screening of antibody-antigen interactions. Nat Biotechnol 18:989–994. doi:10.1038/79494

    Google Scholar 

  42. Strachan G, McElhiney J, Drever MR et al (2002) Rapid selection of anti-hapten antibodies isolated from synthetic and semi-synthetic antibody phage display libraries expressed in Escherichia coli. FEMS Microbiol Lett 210:257–261

    CAS  Google Scholar 

  43. Pini A, Pini A, Viti F, Santucci A, Carnemolla B, Zardi L, Neri PND (1998) Design and Use of a Phage Display Library. Human antibodies with subnanomolar affinity against a marker of angiogenesis eluted from a two-dimensional gel. J Biol Chem 273:21769–21776. doi:10.1074/jbc.273.34.21769

    CAS  Google Scholar 

  44. Lauer B, Ottleben I, Jacobsen H-J, Reinard T (2005) Production of a single-chain variable fragment antibody against fumonisin B1. J Agric Food Chem 53:899–904. doi:10.1021/jf048651s

    CAS  Google Scholar 

  45. Prassler J, Thiel S, Pracht C et al (2011) HuCAL PLATINUM, a synthetic Fab library optimized for sequence diversity and superior performance in mammalian expression systems. J Mol Biol 413:261–278. doi:10.1016/j.jmb.2011.08.012

    CAS  Google Scholar 

  46. Carlsson R, Söderlind E (2001) n-CoDeR concept: unique types of antibodies for diagnostic use and therapy. Expert Rev Mol Diagn 1:102–108. doi:10.1586/14737159.1.1.102

    CAS  Google Scholar 

  47. Persson H, Wallmark H, Ljungars A et al (2008) In vitro evolution of an antibody fragment population to find high-affinity hapten binders. Protein Eng Des Sel 21:485–493. doi:10.1093/protein/gzn024

    CAS  Google Scholar 

  48. Moghaddam A, Løbersli I, Gebhardt K et al (2001) Selection and characterisation of recombinant single-chain antibodies to the hapten Aflatoxin-B1 from naive recombinant antibody libraries. J Immunol Methods 254:169–181

    CAS  Google Scholar 

  49. Van Wyngaardt W, Malatji T, Mashau C et al (2004) A large semi-synthetic single-chain Fv phage display library based on chicken immunoglobulin genes. BMC Biotechnol 4:6. doi:10.1186/1472-6750-4-6

    Google Scholar 

  50. Tanha J, Xu P, Chen Z et al (2001) Optimal design features of camelized human single-domain antibody libraries. J Biol Chem 276:24774–24780. doi:10.1074/jbc.M100770200

    CAS  Google Scholar 

  51. Ohtani M, Hikima J, Jung TS et al (2013) Construction of an artificially randomized IgNAR phage display library: screening of variable regions that bind to hen egg white lysozyme. Mar Biotechnol (NY) 15:56–62. doi:10.1007/s10126-012-9456-1

    CAS  Google Scholar 

  52. McElhiney J, Lawton LA (2005) Detection of the cyanobacterial hepatotoxins microcystins. Toxicol Appl Pharmacol 203:219–230. doi:10.1016/j.taap.2004.06.002

    CAS  Google Scholar 

  53. Li P, Zhang Q, Zhang W (2009) Immunoassays for aflatoxins. TrAC Trends Anal Chem 28:1115–1126. doi:10.1016/j.trac.2009.07.003

    CAS  Google Scholar 

  54. Maragos CM (2009) Recent advances in the development of novel materials for mycotoxin analysis. Anal Bioanal Chem 395:1205–1213. doi:10.1007/s00216-009-2728-6

    CAS  Google Scholar 

  55. Brichta J, Hnilova M, Viskovic T (2005) Generation of hapten-specific recombinant antibodies : antibody phage display technology : a review. 2005:231–252

  56. Yuan Q, Clarke JR, Zhou HR et al (1997) Molecular cloning, expression, and characterization of a functional single-chain Fv antibody to the mycotoxin zearalenone. Appl Environ Microbiol 63:263–269

    CAS  Google Scholar 

  57. Lee MG, Yuan QP, Hart LP, Pestka JJ (2001) Enzyme-linked immunosorbent assays of zearalenone using polyclonal, monoclonal and recombinant antibodies. Methods Mol Biol 157:159–170

    CAS  Google Scholar 

  58. Wang S-H, Du X-Y, Lin L et al (2008) Zearalenone (ZEN) detection by a single chain fragment variable (scFv) antibody. World J Microbiol Biotechnol 24:1681–1685. doi:10.1007/s11274-008-9657-y

    CAS  Google Scholar 

  59. European Commission (2007) Commission Regulation (EC) No 1126/2007 of 28 September 2007 amending Regulation (EC) No 1881/2006 setting maximum levels for certain contaminants in foodstuffs as regards Fusarium toxins in maize and maize products. Off J Eur Union L255:14–17

    Google Scholar 

  60. Bennett GA, Nelsen TC, Miller BM (1994) Enzyme-linked immunosorbent assay for detection of zearalenone in corn, wheat, and pig feed: collaborative study. J AOAC Int 77:1500–1509

    CAS  Google Scholar 

  61. He T, Wang Y, Li P et al (2014) Nanobody-based enzyme immunoassay for aflatoxin in agro-products with high tolerance to cosolvent methanol. Anal Chem 86:8873–8880. doi:10.1021/ac502390c

    CAS  Google Scholar 

  62. Wang S-H, Du X-Y, Huang Y-M et al (2007) Detection of deoxynivalenol based on a single-chain fragment variable of the antideoxynivalenol antibody. FEMS Microbiol Lett 272:214–219. doi:10.1111/j.1574-6968.2007.00765.x

    CAS  Google Scholar 

  63. Wang S, Zheng C, Liu Y et al (2008) Construction of multiform scFv antibodies using linker peptide. J Genet Genomics 35:313–316. doi:10.1016/S1673-8527(08)60045-4

    Google Scholar 

  64. Daly S, Dillon P, Manning B et al (2002) Production and Characterization of Murine Single Chain Fv Antibodies to Aflatoxin B 1 Derived From a Pre-immunized Antibody Phage Display Library System. Food Agric Immunol 14:255–274. doi:10.1080/0954010021000096373

    CAS  Google Scholar 

  65. Trombley A, Fan T, LaBudde R (2011) Aflatoxin plate kit. Performance Tested Method 081003. J AOAC Int 94:1519–1530

    CAS  Google Scholar 

  66. Oguri H, Hirama M, Tsumuraya T et al (2003) Synthesis-based approach toward direct sandwich immunoassay for ciguatoxin CTX3C. J Am Chem Soc 125:7608–7612. doi:10.1021/ja034990a

    CAS  Google Scholar 

  67. Nagumo Y, Oguri H, Tsumoto K et al (2004) Phage-display selection of antibodies to the left end of CTX3C using synthetic fragments. J Immunol Methods 289:137–146. doi:10.1016/j.jim.2004.04.003

    CAS  Google Scholar 

  68. Tsumoto K, Yokota A, Tanaka Y et al (2008) Critical contribution of aromatic rings to specific recognition of polyether rings. The case of ciguatoxin CTX3C-ABC and its specific antibody 1C49. J Biol Chem 283:12259–12266. doi:10.1074/jbc.M710553200

    CAS  Google Scholar 

  69. Lehane L, Lewis RJ (2000) Ciguatera: recent advances but the risk remains. Int J Food Microbiol 61:91–125

    CAS  Google Scholar 

  70. Tsumuraya T, Takeuchi K, Yamashita S et al (2012) Development of a monoclonal antibody against the left wing of ciguatoxin CTX1B: thiol strategy and detection using a sandwich ELISA. Toxicon 60:348–357. doi:10.1016/j.toxicon.2012.04.347

    CAS  Google Scholar 

  71. Tsumuraya T, Fujii I, Hirama M (2014) Preparation of anti-ciguatoxin monoclonal antibodies using synthetic haptens: sandwich ELISA detection of ciguatoxins. J AOAC Int 97:373–379

    CAS  Google Scholar 

  72. Hu X, O’Dwyer R, Wall JG (2005) Cloning, expression and characterisation of a single-chain Fv antibody fragment against domoic acid in Escherichia coli. J Biotechnol 120:38–45. doi:10.1016/j.jbiotec.2005.05.018

    CAS  Google Scholar 

  73. Shaw I, O’Reilly A, Charleton M, Kane M (2008) Development of a high-affinity anti-domoic acid sheep scFv and its use in detection of the toxin in shellfish. Anal Chem 80:3205–3212. doi:10.1021/ac7024199

    CAS  Google Scholar 

  74. Finlay WJJ, Shaw I, Reilly JP, Kane M (2006) Generation of high-affinity chicken single-chain Fv antibody fragments for measurement of the pseudonitzschia pungens toxin domoic acid. Appl Environ Microbiol 72:3343–3349. doi:10.1128/AEM.72.5.3343

    CAS  Google Scholar 

  75. Wang T, Ding H, Yang L et al (2009) Screening and identification of a single chain antibody fragment. Acta Microbiol Sin 49:135–140

    CAS  Google Scholar 

  76. Yang L, Ding H, Gu Z et al (2009) Selection of single chain fragment variables with direct coating of aflatoxin B1 to enzyme-linked immunosorbent assay plates. J Agric Food Chem 57:8927–8932. doi:10.1021/jf9019536

    CAS  Google Scholar 

  77. Yang L, Zhang Y, Ding H et al (2009) Expression and optimization of anti-AFB1 scFv in Escherichia colil. Acta Microbiol Sin 49:880–888

    CAS  Google Scholar 

  78. Rangnoi K, Jaruseranee N, O’Kennedy R et al (2011) One-step detection of aflatoxin-B(1) using scFv-alkaline phosphatase-fusion selected from human phage display antibody library. Mol Biotechnol 49:240–249. doi:10.1007/s12033-011-9398-2

    CAS  Google Scholar 

  79. Hara Y, Dong J, Ueda H (2013) Open-sandwich immunoassay for sensitive and broad-range detection of a shellfish toxin gonyautoxin. Anal Chim Acta 793:107–113. doi:10.1016/j.aca.2013.07.024

    CAS  Google Scholar 

  80. Kawatsu K, Hamano Y, Sugiyama A et al (2002) Development and application of an enzyme immunoassay based on a monoclonal antibody against gonyautoxin components of paralytic shellfish poisoning toxins. J Food Prot 65:1304–1308

    CAS  Google Scholar 

  81. Fraga M, Vilariño N, Louzao MCC et al (2012) Detection of paralytic shellfish toxins by a solid-phase inhibition immunoassay using a microsphere-flow cytometry system. Anal Chem 84:4350–4356. doi:10.1021/ac203449f

    CAS  Google Scholar 

  82. Fonfría ES, Vilariño N, Campbell K et al (2007) Paralytic shellfish poisoning detection by surface plasmon resonance-based biosensors in shellfish matrixes. Anal Chem 79:6303–6311. doi:10.1021/ac070362q

    Google Scholar 

  83. Campbell K, Rawn DFK, Niedzwiadek B, Elliott CT (2011) Paralytic shellfish poisoning (PSP) toxin binders for optical biosensor technology: problems and possibilities for the future: a review. Food Addit Contam Part A Chem Anal Control Expo Risk Assess 28:711–725. doi:10.1080/19440049.2010.531198

    CAS  Google Scholar 

  84. European Commission (2004) Regulation (EC) No 853/2004 of the European Parliament and of the Council of 29 April 2004 laying down specific hygiene rules for on the hygiene of foodstuffs. Off J Eur Union L139:55–206

    Google Scholar 

  85. European Food Safety Authority (EFSA) (2009) Scientific opinion of the panel on contaminants in the food chain on a request from the European Commission on marine biotoxins in shellfish – saxitoxin group. EFSA J 1019:1–3. doi:10.2903/j.efsa.2010.1677.Available

    Google Scholar 

  86. Suzuki T, Munakata Y, Morita K et al (2007) Sensitive Detection of Estrogenic Mycotoxin Zearalenone by Open Sandwich Immunoassay. Anal Sci 23:65–70. doi:10.2116/analsci.23.65

    Google Scholar 

  87. Ihara M, Suzuki T, Kobayashi N et al (2009) Open-sandwich enzyme immunoassay for one-step noncompetitive detection of corticosteroid 11-deoxycortisol. Anal Chem 81:8298–8304. doi:10.1021/ac900700a

    CAS  Google Scholar 

  88. Dong J, Ihara M, Ueda H (2009) Antibody Fab display system that can perform open-sandwich ELISA. Anal Biochem 386:36–44. doi:10.1016/j.ab.2008.11.045

    CAS  Google Scholar 

  89. Liu X, Eichenberger M, Fujioka Y et al (2012) Improved detection sensitivity and selectivity attained by open-sandwich selection of an anti-estradiol antibody. Anal Sci 28:861–867

    Google Scholar 

  90. Huovinen T, Syrjänpää M, Sanmark H et al (2013) Two ScFv antibody libraries derived from identical VL-VH framework with different binding site designs display distinct binding profiles. Protein Eng Des Sel 26:683–693. doi:10.1093/protein/gzt037

    CAS  Google Scholar 

  91. Perkin Elmer (2010) Unmatched Sensitivity Time after Time. DELFIA TRF Technol 1–12

  92. Edupuganti SR, Edupuganti OP, Hearty S, O’Kennedy R (2013) A highly stable, sensitive, regenerable and rapid immunoassay for detecting aflatoxin B1 in corn incorporating covalent AFB1 immobilization and a recombinant Fab antibody. Talanta 115:329–335. doi:10.1016/j.talanta.2013.05.012

    CAS  Google Scholar 

  93. Dunne L, Daly S, Baxter A et al (2005) Surface Plasmon Resonance‐Based Immunoassay for the Detection of Aflatoxin B 1 Using Single‐Chain Antibody Fragments. Spectrosc Lett 38:229–245. doi:10.1081/SL-200058689

    CAS  Google Scholar 

  94. European Commission (2010) Commission Regulation (EU) No 165/2010 of 26 February 2010 amending Regulation (EC) No 1881/2006 setting maximum levels for certain contaminants in foodstuffs as regards aflatoxins. Off J Eur Union L50:8–12

    Google Scholar 

  95. Edupuganti SR, Edupuganti OP, O’Kennedy R (2013) Biological and synthetic binders for immunoassay and sensor-based detection: generation and characterisation of an anti-AFB2 single-chain variable fragment (scFv). World Mycotoxin J 6:273–280. doi:10.3920/WMJ2012.1523

    CAS  Google Scholar 

  96. Zhang D, Li P, Zhang Q et al (2009) Production of ultrasensitive generic monoclonal antibodies against major aflatoxins using a modified two-step screening procedure. Anal Chim Acta 636:63–69. doi:10.1016/j.aca.2009.01.010

    CAS  Google Scholar 

  97. Li X, Li P, Lei J et al (2014) A simple strategy to obtain ultra-sensitive single-chain fragment variable antibodies for aflatoxin detection. RSC Adv 3:22367. doi:10.1039/c3ra42706d

    Google Scholar 

  98. Fischer WJ, Garthwaite I, Miles CO et al (2001) Congener-independent immunoassay for microcystins and nodularins. Environ Sci Technol 35:4849–4856

    CAS  Google Scholar 

  99. Zeck A, Weller MG, Bursill D, Niessner R (2001) Generic microcystin immunoassay based on monoclonal antibodies against Adda. Analyst 126:2002–2007

    CAS  Google Scholar 

  100. Mcelhiney J, Drever M, Lawton LA, Porter AJ (2002) Rapid Isolation of a Single-Chain Antibody against the Cyanobacterial Toxin Microcystin-LR by Phage Display and Its Use in the Immunoaffinity Concentration of Microcystins from Water. Appl Environ Microbiol 68:5288–5295. doi:10.1128/AEM.68.11.5288

    CAS  Google Scholar 

  101. Alvarenga LM, Muzard J, Ledreux A et al (2014) Colorimetric engineered immunoprobe for the detection and quantification of microcystins. J Immunol Methods 406:124–130. doi:10.1016/j.jim.2014.02.014

    CAS  Google Scholar 

  102. Zou L, Xu Y, Li Y et al (2014) Development of a single-chain variable fragment antibody-based enzyme-linked immunosorbent assay for determination of fumonisin B1 in corn samples. J Sci Food Agric 94:1865–1871. doi:10.1002/jsfa.6505

    CAS  Google Scholar 

  103. European Commission (2002) Commission Decision of 12 August 2002 implementing Council Directive 96/23/EC concerning the performance of analytical methods and the interpretation of results. Off J Eur Communities L221:8–36

    Google Scholar 

  104. McGrath TF, Elliott CT, Fodey TL (2012) Biosensors for the analysis of microbiological and chemical contaminants in food. Anal Bioanal Chem 403:75–92. doi:10.1007/s00216-011-5685-9

    CAS  Google Scholar 

  105. Lacy A, Dunne L, Fitzpatrick B et al (2006) Rapid analysis of coumarins using surface plasmon resonance. J AOAC Int 89:884–892

    CAS  Google Scholar 

  106. Daly SJ, Keating GJ, Dillon PP et al (2000) Development of surface plasmon resonance-based immunoassay for aflatoxin B(1). J Agric Food Chem 48:5097–5104

    CAS  Google Scholar 

  107. Hu X, Spada S, White S et al (2006) Adsorption and activity of a domoic acid binding antibody fragment on mesoporous silicates. J Phys Chem B 110:18703–18709. doi:10.1021/jp062423e

    CAS  Google Scholar 

  108. Hu X, O’Hara L, White S et al (2007) Optimisation of production of a domoic acid-binding scFv antibody fragment in Escherichia coli using molecular chaperones and functional immobilisation on a mesoporous silicate support. Protein Expr Purif 52:194–201. doi:10.1016/j.pep.2006.08.009

    CAS  Google Scholar 

  109. Hortigüela MJ, Wall JG (2013) Improved detection of domoic acid using covalently immobilised antibody fragments. Mar Drugs 11:881–895. doi:10.3390/md11030881

    Google Scholar 

  110. Min W-K, Kweon D-H, Park K et al (2011) Characterisation of monoclonal antibody against aflatoxin B1 produced in hybridoma 2C12 and its single-chain variable fragment expressed in recombinant Escherichia coli. Food Chem 126:1316–1323. doi:10.1016/j.foodchem.2010.11.088

    CAS  Google Scholar 

  111. Li P, Zhang Z, Zhang Q et al (2012) Current development of microfluidic immunosensing approaches for mycotoxin detection via capillary electromigration and lateral flow technology. Electrophoresis 33:2253–2265. doi:10.1002/elps.201200050

    CAS  Google Scholar 

  112. WHO (2008) WHO guidelines for drinking-water quality. In: WHO Geneva (ed) WHO Chron, 3rd edn. WHO Geneva, Geneva, p 195

    Google Scholar 

  113. WHO (1999) Guidelines for safe recreational water environments, vol 1. Coastal and fresh waters, Geneva, pp 136–158

    Google Scholar 

  114. Lawton LA, Chambers H, Edwards C et al (2010) Rapid detection of microcystins in cells and water. Toxicon 55:973–978. doi:10.1016/j.toxicon.2009.05.030

    CAS  Google Scholar 

  115. Kim YM, Oh SW, Jeong SY et al (2003) Development of an ultrarapid one-step fluorescence immunochromatographic assay system for the quantification of microcystins. Environ Sci Technol 37:1899–1904

    CAS  Google Scholar 

  116. Lattanzio VMT, Nivarlet N, Lippolis V et al (2012) Multiplex dipstick immunoassay for semi-quantitative determination of Fusarium mycotoxins in cereals. Anal Chim Acta 718:99–108. doi:10.1016/j.aca.2011.12.060

    CAS  Google Scholar 

  117. McElhiney J, Lawton LA, Porter AJR (2000) Detection and quantification of microcystins (cyanobacterial hepatotoxins) with recombinant antibody fragments isolated from a naive human phage display library. FEMS Microbiol Lett 193:83–88. doi:10.1111/j.1574-6968.2000.tb09406.x

    CAS  Google Scholar 

  118. Choi G-H, Lee D-H, Min W-K et al (2004) Cloning, expression, and characterization of single-chain variable fragment antibody against mycotoxin deoxynivalenol in recombinant Escherichia coli. Protein Expr Purif 35:84–92. doi:10.1016/j.pep.2003.12.008

    CAS  Google Scholar 

  119. Doyle PJ, Arbabi-Ghahroudi M, Gaudette N et al (2008) Cloning, expression, and characterization of a single-domain antibody fragment with affinity for 15-acetyl-deoxynivalenol. Mol Immunol 45:3703–3713. doi:10.1016/j.molimm.2008.06.005

    CAS  Google Scholar 

  120. Van Houwelingen A, De Saeger S, Rusanova T et al (2008) Generation of recombinant alpaca VHH antibody fragments for the detection of the mycotoxin ochratoxin A. World Mycotoxin J 1:407–417. doi:10.3920/WMJ2008.1070

    Google Scholar 

  121. Min W-K, Cho Y-J, Park J-B et al (2010) Production and characterization of monoclonal antibody and its recombinant single chain variable fragment specific for a food-born mycotoxin, fumonisin B1. Bioprocess Biosyst Eng 33:109–115. doi:10.1007/s00449-009-0350-9

    CAS  Google Scholar 

  122. Tuomas H, Yuan LIU, Xian-jin LIU, et al. (2012) Screening and Identification of Single-Chain Antibodies Against Microcystin-LR by Magnetic Beads and Time Resolved Fluorescence Immunoassay. 45:330–337. doi:10.3864/j.issn.0578-1752.2012.02.015

  123. Food and Drug Administration (FDA) (2000) Guidance for Industry : Action Levels for Poisonous or Deleterious Substances in Human Food and Animal Feed. In: Food Guid. Doc. http://www.fda.gov/Food/GuidanceRegulation/GuidanceDocumentsRegulatoryInformation/ChemicalContaminantsMetalsNaturalToxinsPesticides/ucm077969.htm

  124. FAO (2004) 3.4.1 Worldwide limits for aflatoxins. Worldw. Regul. mycotoxins food Feed 2003. Food and Agriculture Organisation of the United Nations, pp 17–22

  125. Yu F-Y, Gribas AV, Vdovenko MM, Sakharov IY (2013) Development of ultrasensitive direct chemiluminescent enzyme immunoassay for determination of aflatoxin B1 in food products. Talanta 107:25–29. doi:10.1016/j.talanta.2012.12.047

    CAS  Google Scholar 

  126. Van der Gaag B, Spath S, Dietrich H et al (2003) Biosensors and multiple mycotoxin analysis. Food Control 14:251–254. doi:10.1016/S0956-7135(03)00008-2

    Google Scholar 

  127. European Commission (2006) Commission regulation (EC) No 401/2006 of 23 February 2006 laying down the methods of sampling and analysis for the official control of the levels of mycotoxins in foodstuffs. Off J Eur Union L70:12–34

    Google Scholar 

  128. FAO (2004) 3.4.2 Worldwide limits for other mycotoxins. Worldw. Regul. mycotoxins food Feed 2003. Food and Agriculture Organisation of the United Nations, pp 23–26

  129. Food and Drug Administration (FDA) (2008) Chapter 7. Molecular biology and natural toxins. FDA Compliance Progr. Guid. Man. Progr. 7307.001. pp 1–3

  130. Sheng Y, Jiang W, De Saeger S et al (2012) Development of a sensitive enzyme-linked immunosorbent assay for the detection of fumonisin B1 in maize. Toxicon 60:1245–1250. doi:10.1016/j.toxicon.2012.08.011

    CAS  Google Scholar 

  131. Shiu C-M, Wang J-J, Yu F-Y (2010) Sensitive enzyme-linked immunosorbent assay and rapid one-step immunochromatographic strip for fumonisin B1 in grain-based food and feed samples. J Sci Food Agric 90:1020–1026. doi:10.1002/jsfa.3911

    CAS  Google Scholar 

  132. European Commission (2010) Commission Regulation (EC) No 1881/2006 of 19 December 2006 setting maximum levels for certain contaminants in foodstuffs. Off J Eur Union L364:5–24

    Google Scholar 

  133. Zhang A, Ma Y, Feng L et al (2011) Development of a sensitive competitive indirect ELISA method for determination of ochratoxin A levels in cereals originating from Nanjing, China. Food Control 22:1723–1728. doi:10.1016/j.foodcont.2011.04.004

    CAS  Google Scholar 

  134. Yu F-Y, Chi T-F, Liu B-H, Su C-C (2005) Development of a sensitive enzyme-linked immunosorbent assay for the determination of ochratoxin A. J Agric Food Chem 53:6947–6953. doi:10.1021/jf0513922

    CAS  Google Scholar 

  135. Cha S-H, Kim S-H, Bischoff K et al (2012) Production of a highly group-specific monoclonal antibody against zearalenone and its application in an enzyme-linked immunosorbent assay. J Vet Sci 13:119–125

    Google Scholar 

  136. Metcalf J, Bell S, Codd G (2000) Production of novel polyclonal antibodies against the cyanobacterial toxin microcystin-LR and their application for the detection and quantification of microcystins and nodularin. Water Res 34:2761–2769. doi:10.1016/S0043-1354(99)00429-7

    CAS  Google Scholar 

  137. Rapala J, Erkomaa K, Kukkonen J et al (2002) Detection of microcystins with protein phosphatase inhibition assay, high-performance liquid chromatography – UV detection and enzyme-linked immunosorbent assay Comparison of methods. Anal Chim Acta 466:213–231

    CAS  Google Scholar 

  138. Sheng J-W, He M, Shi H-C (2007) A highly specific immunoassay for microcystin-LR detection based on a monoclonal antibody. Anal Chim Acta 603:111–118. doi:10.1016/j.aca.2007.09.029

    CAS  Google Scholar 

  139. European Commission (2002) Commission Decision establishing special health checks for the harvesting and processing of certain bivalve molluscs with a level of amnesic shellfish poison (ASP) exceeding the limit laid down by Council Directive 91/492/EEC. Off J Eur Communities L75:65–66

    Google Scholar 

  140. Kawatsu K, Hamano Y, Noguchi T (1999) Production and characterization of a monoclonal antibody against domoic acid and its application to enzyme immunoassay. Toxicon 37:1579–1589

    CAS  Google Scholar 

  141. Garthwaite I, Ross KM, Miles CO et al (1998) Polyclonal antibodies to domoic acid, and their use in immunoassays for domoic acid in Sea Water and Shellfish. Nat Toxins 6:93–104

    CAS  Google Scholar 

  142. Pepper LR, Cho YK, Boder ET, Shusta EV (2008) A decade of yeast surface display technology: where are we now? Comb Chem High Throughput Screen 11:127–134

    CAS  Google Scholar 

  143. Boder ET, Raeeszadeh-Sarmazdeh M, Price JV (2012) Engineering antibodies by yeast display. Arch Biochem Biophys 526:99–106. doi:10.1016/j.abb.2012.03.009

    CAS  Google Scholar 

  144. Borrebaeck CAK, Wingren C (2011) Recombinant antibodies for the generation of antibody arrays. Methods Mol Biol 785:247–262. doi:10.1007/978-1-61779-286-1_17

    CAS  Google Scholar 

  145. THoen PAC, Jirka SMG, Ten Broeke BR et al (2012) Phage display screening without repetitious selection rounds. Anal Biochem 421:622–631. doi:10.1016/j.ab.2011.11.005

    CAS  Google Scholar 

  146. Glanville J, Zhai W, Berka J et al (2009) Precise determination of the diversity of a combinatorial antibody library gives insight into the human immunoglobulin repertoire. Proc Natl Acad Sci U S A 106:20216–20221. doi:10.1073/pnas.0909775106

    CAS  Google Scholar 

  147. Ravn U, Gueneau F, Baerlocher L et al (2010) By-passing in vitro screening–next generation sequencing technologies applied to antibody display and in silico candidate selection. Nucleic Acids Res 38:e193. doi:10.1093/nar/gkq789

    CAS  Google Scholar 

  148. D’Angelo S, Glanville J, Ferrara F et al (2014) The antibody mining toolbox: An open source tool for the rapid analysis of antibody repertoires. MAbs 6:160–172. doi:10.4161/mabs.27105

    Google Scholar 

  149. Heffner KM, Hizal DB, Kumar A et al (2014) Exploiting the proteomics revolution in biotechnology: from disease and antibody targets to optimizing bioprocess development. Curr Opin Biotechnol 30:80–86. doi:10.1016/j.copbio.2014.06.006

    CAS  Google Scholar 

  150. Cheung WC, Beausoleil SA, Zhang X et al (2012) A proteomics approach for the identification and cloning of monoclonal antibodies from serum. Nat Biotechnol 30:447–452. doi:10.1038/nbt.2167

    CAS  Google Scholar 

  151. Wine Y, Boutz DR, Lavinder JJ et al (2013) Molecular deconvolution of the monoclonal antibodies that comprise the polyclonal serum response. Proc Natl Acad Sci U S A 110:2993–2998. doi:10.1073/pnas.1213737110

    CAS  Google Scholar 

  152. European Commission (2010) Directive 2010/63/EU of the European Parliament and of the Council on the protection of animals used for scientific purposes. Off J Eur Union L276:33–79

    Google Scholar 

  153. Meneely JP, Ricci F, van Egmond HP, Elliott CT (2011) Current methods of analysis for the determination of trichothecene mycotoxins in food. TrAC Trends Anal Chem 30:192–203. doi:10.1016/j.trac.2010.06.012

    CAS  Google Scholar 

  154. Weller M (2013) Immunoassays and Biosensors for the Detection of Cyanobacterial Toxins in Water. Sensors 13:15085–15112. doi:10.3390/s131115085

    Google Scholar 

  155. Meulenberg EP (2012) Immunochemical methods for ochratoxin A detection: a review. Toxins (Basel) 4:244–266. doi:10.3390/toxins4040244

    CAS  Google Scholar 

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Acknowledgements

The research leading to these results has received funding from the European Union's Seventh Framework Programme managed by REA Research Executive Agency http://ec.eiiiOpa.eu/research/rea(FP7/2007-2013) under grant agreement no [315285].

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Kavanagh, O., Elliott, C.T. & Campbell, K. Progress in the development of immunoanalytical methods incorporating recombinant antibodies to small molecular weight biotoxins. Anal Bioanal Chem 407, 2749–2770 (2015). https://doi.org/10.1007/s00216-015-8502-z

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