Transferring the Selectivity of a Natural Antibody into a Molecularly Imprinted Polymer

Part of the Methods in Molecular Biology book series (MIMB, volume 1575)


Natural antibodies are widely used for their unprecedented reproducibility and the remarkable selectivity for a wide range of analytes. However, biodegradability and the need to work in biocompatible environments limit their applications. Molecularly imprinted polymers are a robust alternative. While molecularly imprinted polymers have shown remarkable selectivities for small molecules, large structures as proteins, viruses or entire cells are still problematic and flexible structures are virtually impossible to imprint. We have developed a method to form a polymeric copy of the antibodies instead. This book chapter aims to summarize the progress with this technique. To make it easier for other scientists to use this methods I critically discuss advantages and drawbacks of the method compared to alternative techniques. The discussion should help to identify for which applications this technique would be valuable. Finally, I provide a practical guide to use this new method. I highlight potential problems and give hints for possible improvements or adaptations for different applications.

Key words

Imprinting Molecularly imprinted polymers Synthetic antibodies Artificial binding sites 


  1. 1.
    Ionescu R, Vlasak J (2010) Kinetics of chemical degradation in monoclonal antibodies: relationship between rates at the molecular and peptide levels. Anal Chem 82:3198–3206CrossRefPubMedGoogle Scholar
  2. 2.
    Ye L, Mosbach K (2008) Molecular imprinting: synthetic materials as substitutes for biological antibodies and receptors. Chem Mater 20:859–868CrossRefGoogle Scholar
  3. 3.
    O’Mahony J, Karlsson BCG, Mizaikoff B, Nicholls IA (2007) Correlated theoretical, spectroscopic and X-ray crystallographic studies of a non-covalent molecularly imprinted polymerisation system. Analyst 132:1161–1168CrossRefPubMedGoogle Scholar
  4. 4.
    Wei S, Jakusch M, Mizaikoff B (2007) Investigating the mechanisms of 17β-estradiol imprinting by computational prediction and spectroscopic analysis. Anal Bioanal Chem 389:423–431CrossRefPubMedGoogle Scholar
  5. 5.
    Singh K, Balasubramanian S, Amitha Rani BE (2012) Computational and experimental studies of molecularly imprinted polymers for organochlorine pesticides heptachlor and DDT. Curr Anal Chem 8(4):562–568CrossRefGoogle Scholar
  6. 6.
    Ho W-L, Liu Y-Y, Lin T-C (2011) Development of molecular imprinted polymer for selective adsorption of benz[a]pyrene among airborne polycyclic aromatic hydrocarbon compounds. Environ Eng Sci 28(6):421–434CrossRefGoogle Scholar
  7. 7.
    Andersson L, Mosbach K (1990) Enantiomeric resolution on molecularly imprinted polymers prepared with only non-covalent and non-ionic interactions. J Chromatogr 516:313–322CrossRefPubMedGoogle Scholar
  8. 8.
    Whitcombe, M. J.; Rodriguez, M. E.; Villar, P.; Vulfson, E. N., A new method for the introduction of recognition site functionality into polymers prepared by molecular imprinting: synthesis and characterization of polymeric receptors for cholesterol, J Am Chem Soc 1995, 117, 7105–7111Google Scholar
  9. 9.
    Vlatakis G, Andersson LI, Müller RI, Mosbach K (1993) Drug assay using antibody mimics made by molecular imprinting. Nature 361:645–647CrossRefPubMedGoogle Scholar
  10. 10.
    Kellens E, Bove H, Conradi M, D’Olieslaeger L, Wagner P, Landfester K, Junkers T, Ethirajan A (2016) Improved molecular imprinting based on colloidal particles made from miniemulsion: a case study on testosterone and its structural analogues. Macromolecules 49:2559–2567CrossRefGoogle Scholar
  11. 11.
    Peeters M, Kobben S, Jimenez-Monroy KL, Modesto L, Kraus M, Vandenryt T, Gaulke A, van Grinsven B, Ingebrandt S, Junkers T, Wagner P (2014) Thermal detection of histamine with a graphene oxide based molecularly imprinted polymer platform prepared by reversible addition–fragmentation chain transfer polymerization. Sens Actuators B Chem 203:527–535CrossRefGoogle Scholar
  12. 12.
    Liu J, Deng Q, Tao D, Yang K, Zhang L, Liang Z, Zhang Y (2014) Preparation of protein imprinted materials by hierarchical imprinting techniques and application in selective depletion of albumin from human serum. Sci Rep 4:5487PubMedPubMedCentralGoogle Scholar
  13. 13.
    Wangchareansak T, Sangma C, Choowongkomon K, Dickert FL, Lieberzeit P (2011) Surface molecular imprints of WGA lectin as artificial receptors for mass-sensitive binding studies. Anal Bioanal Chem 400:2499–2506CrossRefPubMedGoogle Scholar
  14. 14.
    Bolisay LD, Culver JN, Kofinas P (2007) Optimization of virus imprinting methods to improve selectivity and reduce nonspecific binding. Biomacromolecules 8(12):3893–3899CrossRefPubMedGoogle Scholar
  15. 15.
    Birnbaumer GM, Lieberzeit PA, Richter L, Schirhagl R, Milnera M, Dickert FL, Bailey A, Ertl P (2009) Detection of viruses with molecularly imprinted polymers integrated on a microfluidic biochip using contact-less dielectric microsensors. Lab Chip 6:3549–3556CrossRefGoogle Scholar
  16. 16.
    Cumbo A, Lorber B, Corvini PF-X, Meier W, Shahgaldian P (2012) A synthetic nanomaterial for virus recognition produced by surface imprinting. Nat Commun 4:1503CrossRefGoogle Scholar
  17. 17.
    Bai W, Spivak DA (2014) A double imprinted diffraction grating sensor based on a virus responsive super aptamer hydrogel derived from an impure extract. Angew Chem Int Ed 53:2095–2098CrossRefGoogle Scholar
  18. 18.
    Schirhagl R, Hall EW, Fuereder I, Zare RN (2012) Separation of bacteria with imprinted polymeric films. Analyst 137(6):1495–1499CrossRefPubMedGoogle Scholar
  19. 19.
    Darder M, Aranda P, Burgos-Asperilla L, Llobera A, Cadarso VJ, Sanchez CF, Ruiz-Hitzky E (2010) Algae–silica systems as functional hybrid materials. J Mater Chem 20:9362–9369CrossRefGoogle Scholar
  20. 20.
    Eersels K, van Grinsven B, Khorshid M, Somers V, Püttmann C, Stein C, Barth S, Dilien H, Bos GMJ, Germeraad WTV, Cleij TJ, Thoelen R, De Ceuninck W, Wagner P (2015) Heat-transfer-method-based cell culture quality assay through cell detection by surface imprinted polymers. Langmuir 31:2043–2050CrossRefPubMedGoogle Scholar
  21. 21.
    Schirhagl R, Ren K, Zare RN (2012) Surface-imprinted polymers in microfluidic devices. Sci China Chem 55(4):469–483CrossRefGoogle Scholar
  22. 22.
    Schirhagl R (2014) Bioapplications for molecularly imprinted polymers. Anal Chem 86(1):250–261CrossRefPubMedGoogle Scholar
  23. 23.
    Sindhu Sharma P, Iskierko Z, Pietrzyk-Le A, D'Souza F, Kutner W (2015) Bioinspired intelligent molecularly imprinted polymerss for chemosensing: a mini review. Electrochem Commun 50:81–87CrossRefGoogle Scholar
  24. 24.
    Haupt K, Mosbach K (2000) Molecularly imprinted polymers and their use in biomimetic sensors. Chem Rev 100(7):2495–2504CrossRefPubMedGoogle Scholar
  25. 25.
    Lorenzo RA, Carro AM, Alvarez-Lorenzo C, Concheiro A (2011) To remove or not to remove? The challenge of extracting the template to make the cavities available in molecularly imprinted polymers (MIPs). Int J Mol Sci 12(7):4327–4347CrossRefPubMedPubMedCentralGoogle Scholar
  26. 26.
    Mosbach K, Yu Y, Andersch J, Ye L (2001) Generation of new enzyme inhibitors using imprinted binding sites: the anti-idiotypic approach, a step toward the next generation of molecular imprinting. J Am Chem Soc 123:12420–12421CrossRefPubMedGoogle Scholar
  27. 27.
    Patent application, WO 1995021673 A1, preparation and application of artificial anti-idiotypic imprintsGoogle Scholar
  28. 28.
    Eichelbaum F, Borngraber R, Schroder J, Lucklum R, Hauptmann P (1999) Interface circuits for quartz-crystal-microbalance sensors. Rev Sci Instrum 70:2537CrossRefGoogle Scholar
  29. 29.
    Schirhagl R, Lieberzeit PA, Dickert FL (2010) Chemosensors for viruses based on artificial immunoglobulin copies. Adv Mater 22:2078–2081CrossRefPubMedGoogle Scholar
  30. 30.
    Sikorski AF, Daczyńska RB (1982) Fluorescent labelling of proteins on thin layers of solid dansyl chloride. Biochim Biophys Acta Biomembr 690(2):302–305CrossRefGoogle Scholar
  31. 31.
    Dickert FL, Hayden O, Bindeus R, Mann K-J, Blaas D, Waigmann E (2004) Bioimprinted QCM sensors for virus detection-screening of plant sap. Anal Bioanal Chem 378:1929CrossRefPubMedGoogle Scholar
  32. 32.
    Schirhagl R, Seifner A, Husain FT, Cichna-Markl M, Lieberzeit PA, Dickert FL (2010) Antibodies and their replicae in microfluidic sensor systems—labelfree quality assessment in food chemistry and medicine. Sensor Lett 8:399–404CrossRefGoogle Scholar
  33. 33.
    Schirhagl R, Qian J, Dickert FL (2012) Immunosensing with artificial antibodies in organic solvents or complex matrices. Sens Actuators B 173:585–590CrossRefGoogle Scholar
  34. 34.
    Schirhagl R, Latif U, Dickert FL (2011) Atrazine detection based on antibody replicas. J Mater Chem 21(38):14594–14598CrossRefGoogle Scholar
  35. 35.
    Dickert FL, Lieberzeit PA, Achatz P, Palfinger C, Fassnauer M, Schmid E, Werther W, Horner G (2004) QCM array for on-line-monitoring of composting procedures. Analyst 129:432–437CrossRefPubMedGoogle Scholar
  36. 36.
    Iqbal N, Mustafa G, Rehman A, Biedermann A, Najafi B, Lieberzeit PA, Dickert FL (2010) QCM-arrays for sensing terpenes in fresh and dried herbs via bio-mimetic MIP layers. Sensors 10(7):6361–6376CrossRefPubMedPubMedCentralGoogle Scholar
  37. 37.
    Latif U, Mujahid A, Afzal A, Sikorski R, Lieberzeit PA, Dickert FL (2011) Dual and tetraelectrode QCMs using imprinted polymers as receptors for ions and neutral analytes. Anal Bioanal Chem 400:2507–2515CrossRefPubMedGoogle Scholar
  38. 38.
    Seidler K, Polreichova M, Lieberzeit PA, Dickert FL (2009) Biomimetic yeast cell typing—application of QCMs. Sensors 9(10):8146–8157CrossRefPubMedPubMedCentralGoogle Scholar
  39. 39.
    Lieberzeit PA, Rehman A, Najafi B, Dickert FL (2008) Real-life application of a QCM-based e-nose: quantitative characterization of different plant-degradation processes. Anal Bioanal Chem 391:2897–2903CrossRefPubMedGoogle Scholar
  40. 40.
    Schirhagl R, Podlipna D, Lieberzeit PA, Dickert FL (2010) Comparing biomimetic and biological receptors for insulin sensing. Chem Commun 46:3128–3130CrossRefGoogle Scholar
  41. 41.
    Nishino H, Huang CS, Shea KJ (2006) Selective protein capture by epitope imprinting. Angew Chem Int Ed Engl 45(15):2392–2396CrossRefPubMedGoogle Scholar
  42. 42.
    Zhang Y, Deng C, Liu S, Wu J, Chen Z, Li C, Lu W (2015) Active targeting of tumors through conformational epitope imprinting. Angew Chem Int Ed Engl 54(17):5157–5160CrossRefPubMedGoogle Scholar
  43. 43.
    Zhao X-L, Li D-Y, He X-W, Li W-Y, Zhang Y-K (2014) An epitope imprinting method on the surface of magnetic nanoparticles for specific recognition of bovine serum album. J Mater Chem B 2:7575–7582CrossRefGoogle Scholar
  44. 44.
    Wackerlig J, Schirhagl R (2016) Applications of molecularly imprinted polymer nanoparticles and their advances toward industrial use: a review. Anal Chem 88(1):250–261CrossRefPubMedGoogle Scholar
  45. 45.
    Jenik M, Schirhagl R, Schirk C, Hayden O, Lieberzeit P, Blaas D, Paul G, Dickert FL (2009) Sensing picornaviruses using molecular imprinting techniques on a quartz crystal microbalance. Anal Chem 81(13):5320–5532CrossRefPubMedGoogle Scholar

Copyright information

© Springer Science+Business Media LLC 2017

Authors and Affiliations

  1. 1.University Medical Center GroningenGroningen UniversityGroningenThe Netherlands

Personalised recommendations