Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • Review Article
  • Published:

The Emerging Technique of Molecular Imprinting and Its Future Impact on Biotechnology

Abstract

The technique of molecular imprinting allows the formation of specific recognition and catalytic sites in macromolecules by the use of templates. Molecularly imprinted polymers have been applied in an increasing number of applications where molecular binding events are of interest. These include (i) the use of molecularly imprinted polymers as tailor-made separation materials, (ii) antibody and receptor binding site mimics in recognition and assay systems, (iii) enzyme mimics for catalytic applications, and (iv) recognition elements in bio-sensors. The stability and low cost of molecularly imprinted polymers make them advantageous for use in analysis as well as in industrial scale production and application.

This is a preview of subscription content, access via your institution

Access options

Buy this article

Prices may be subject to local taxes which are calculated during checkout

Similar content being viewed by others

References

  1. Pauling, L. 1940. A theory of the structure and process of formation of antibodies. J. Am. Chem. Soc. 62: 2643–2657.

    CAS  Google Scholar 

  2. Mosbach, K. and Mosbach, R. 1966. Entrapment of enzymes and microorganisms in synthetic cross-linked polymers and their application in column techniques. Acta. Chem. Scand. 20: 2807–2810.

    CAS  PubMed  Google Scholar 

  3. Wulff, G. 1986. Molecular recognition in polymers prepared by imprinting with templates, p. 186–230. In: Polymeric reagents and catalysts, Vol. 308, FordW. T. (Ed.). Washington, DC, American Chemical Society.

    Google Scholar 

  4. Wulff, G. 1993. The role of binding-site interactions in the molecular imprint-ing of polymers, Trends Biotechnol. 11: 85–87.

    CAS  PubMed  Google Scholar 

  5. Shea, K.J. 1994. Molecular imprinting of synthetic network polymers: the de novo synthesis of macromolecular binding and catalytic sites, Trends Polym. Sci. 19: 9–14.

    Google Scholar 

  6. Arshady, R. and Mosbach, K. 1981. Synthesis of substrate-selective polymers by host-guest polymerization. Makromol. Chem. 182: 687–692.

    CAS  Google Scholar 

  7. Ekberg, B. and Mosbach, K. 1989. Molecular imprinting: a technique for pro-ducing specific separation materials. Trends Biotechnol. 7: 92–96.

    CAS  Google Scholar 

  8. Mosbach, K. 1994. Trends Biochem. Sci. 19: 9–14.

    CAS  PubMed  Google Scholar 

  9. Sellergren, B., Ekberg, B. and Mosbach, K. 1985. Molecular imprinting of amino acid derivatives in macroporous polymers. Demonstration of substrate-and enantio-selectivity by chromatographic resolution of racemic mixtures of amino acid derivatives. J. Chromatogr. 347: 1–10.

    Google Scholar 

  10. Andersson, L.I. and Mosbach, K. 1990. Enantiomeric resolution on molecu-larly imprinted polymers prepared with only non-covalent and non-ionic inter-actions. J. Chromatogr. 516: 313–322.

    CAS  PubMed  Google Scholar 

  11. Dunkin, I.R., Lenfeld, J. and Sherrington, D.C. 1993. Molecular imprinting of flat polycondensed aromatic molecules in macroporous polymers. Polymer 34(1): 77–84.

    CAS  Google Scholar 

  12. Nicholls, I.A., Ramström, O. and Mosbach, K. 1995. Insights into the role of the hydrogen bond and hydrophobic effect on the recognition in molecularly imprinted polymer synthetic peptide receptor mimics. J. Chromatogr. 691: 349–353.

    CAS  Google Scholar 

  13. Ramström, O., Andersson, L.I. and Mosbach, K. 1993.Recognition sites incorporating both pyridinyl and carboxy functionalities prepared by molecu-lar imprinting. J. Org. Chem. 58(26): 7562–7564.

    Google Scholar 

  14. Dhal, P.K. and Arnold, F.H. 1991. Template-mediated synthesis of metal-complexing polymers for molecular recognition. J. Am. Chem. Soc. 113: 7417–7418.

    CAS  Google Scholar 

  15. Mallik, S., Plunkett, S., Dhal, P., Johnson, R., Pack, D., Shnek, D. and Arnold, F. 1994. Towards materials for the specific recognition and separation of pro-teins. New. J. Chem. 18: 299–304.

    CAS  Google Scholar 

  16. Whitcombe, M.J., Rodriguez, M.E. and Vulfson, E.N. 1994. Polymeric adsorbents for cholesterol prepared by molecular imprinting, p. 565–571. In: Separations for Biotechnology 3, Royal Society of Chemistry Special Publication 158.

    Google Scholar 

  17. Whitcombe, M.J., Rodriguez, M.E., Villar, P. and Vulfson, E.N. 1995. A new method for the introduction of recognition site functionality into polymers pre-pared by molecular imprinting: synthesis and characterization of polymeric receptors for cholesterol. J. Am. Chem. Soc. 117: 7105–7111.

    CAS  Google Scholar 

  18. Kempe, M. and Mosbach, K. 1994. Direct resolution of naproxen on a non-covalently molecularly imprinted chiral stationary phase. J. Chromatogr. 664: 276–279.

    CAS  Google Scholar 

  19. Fischer, L., Müller, R., Ekberg, B. and Mosbach, K. 1991. Direct enantiosep-aration of β-adrenergic blockers using a chiral stationary phase prepared by molecular imprinting. J. Am. Chem. Soc. 113: 9358–9360.

    CAS  Google Scholar 

  20. Ramström, O., Cong, Y. and Mosbach, K. 1995. Chiral recognition in adren-ergic receptor binding mimics prepared by molecular imprinting. J. Mol. Recogn. Submitted.

  21. Ramström, O., Nicholls, I.A. and Mosbach, K. 1994. Synthetic peptide recep-tor mimics: highly stereoselective recognition in non-covalent molecularly imprinted polymers. Tetrahedron: Asymmetry 5(4): 649–656.

    Google Scholar 

  22. Kriz, D., Berggren Kriz, C., Andersson, L.I. and Mosbach, K. 1994. Thin-layer chromatography based on the molecular imprinting technique. Anal. Chem. 66: 2636–2639.

    CAS  Google Scholar 

  23. Nilsson, K., Lindell, J., Sellergren, B., Norrlöw, O. and Mosbach, K. 1994. Imprinted polymers as antibody mimetics and new affinity gels for selective separations in capillary electrophoresis. J. Chromatogr. 680: 57–61.

    CAS  Google Scholar 

  24. Vlatakis, G., Andersson, L.I., Müller, R. and Mosbach, K. 1993. Drug assay using antibody mimics made by molecular imprinting. Nature 361: 645–647.

    CAS  PubMed  Google Scholar 

  25. Andersson, L.I., Müller, R., Vlatakis, G. and Mosbach, K. 1995. Mimics of the binding sites of opioid receptors obtained by molecular imprinting of enkephalin and morphine. Proc. Natl. Acad. Sci., USA 92: 4788–4792.

    CAS  PubMed  PubMed Central  Google Scholar 

  26. Lerner, R.A., Benkovic, S.J. and Schultz, P.G. 1991. At the crossroads of chemistry and immunology: catalytic antibodies. Science. 659–667.

    CAS  PubMed  Google Scholar 

  27. Robinson, D.K. and Mosbach, K. 1989. Molecular imprinting of a transition state analogue leads to a polymer exhibiting esterolytic activity. J. Chem. Soc., Chem. Commun., 969–970.

  28. Ohkubo, K., Urata, Y., Hirota, S., Funakoshi, Y., Sagawa, T., Usui, S. and Yoshinaga, K. 1995. Catalytic activities of novel L-histidyl group-introduced polymers imprinted by a transition state analogue in the hydrolysis of amino acid esters. J. Mol. Catal. 101: L111–L114.

    CAS  Google Scholar 

  29. Sellergren, B. and Shea, K.J. 1994. Enantioselective ester hydrolysis cat-alyzed by imprinted polymers. Tetrahedron: Asymmetry 5(8): 1403–1406.

    CAS  Google Scholar 

  30. Andersson, L.I. and Mosbach, K. 1989. Molecular imprinting of the coen-zyme-substrate analogue N-pyridoxyl-L-phenylalaninanilide. Makromol. Chem., Rapid Commun. 10: 491–495.

    CAS  Google Scholar 

  31. Matsui, J., Nicholls, I.A., Karube, I. and Mosbach, K. 1995. Carbon-carbon bond formation using substrate selective catalytic polymers prepared by molecular imprinting: an artificial class II aldolase. J. Org. Chem. In press

  32. Shimada, T., Hirose, R. and Morihara, K. 1994. Footprint catalysis. X.Surface modification of molecular footprint catalysts and its effects on their molecular recognition and catalysis. Bull. Chem. Soc. Jpn. 67: 227–235.

    Google Scholar 

  33. Shokat, K.M., Leumann, C.J., Sugasawara, R., and Schultz, P.G. 1989. A new strategy for the generation of catalytic antibodies. Nature 338: 269.

    CAS  PubMed  Google Scholar 

  34. Müller, R., Andersson, L.I. and Mosbach, K. 1993. Molecularly imprinted polymers facilitating a β-elimination reaction. Makromol. Chem., Rapid Commun. 14: 637–641.

    Google Scholar 

  35. Beach, J.V. and Shea, K.J. 1994. Designed catalysts. A synthetic network polymer that catalyzes the dehydrofluorination of 4-fluoro-4-(p-nitrophenyl) butan-2-one. J. Am. Chem. Soc. 116: 379–380.

    Google Scholar 

  36. Tawfik, D. 1995. Personal communication.

    Google Scholar 

  37. Leonhardt, A. and Mosbach, K. 1987. Enzyme-mimicking polymers exhibit-ing specific substrate binding and catalytic functions. Reactive Polymers 6: 285–290.

    CAS  Google Scholar 

  38. Andersson, L.I., Miyabayashi, A., O'Shannessy, D.J. and Mosbach, K. 1990. Enantiomeric resolution of amino acid derivatives on molecularly imprinted polymers as monitored by potentiometric measurements. J. Chromatogr. 516: 323–331.

    CAS  PubMed  Google Scholar 

  39. Piletskii, S., Parhometz, Y., Lavryk, N., Panasyuk, T. and El'skaya, A. 1994. Sensors for low-weight organic molecules based on molecular imprinting technique. Sensor. Actuator. B 18-19: 629 631.

    Google Scholar 

  40. Kriz, D. and Mosbach, K. 1995. Competitive amperometric morphine sensor based on an agarose immobilised molecularly imprinted polymer. Anal. Chim. Acta 300: 71–75.

    CAS  Google Scholar 

  41. Hedborg, E., Winquist, P., Andersson, L.I. and Mosbach, K. 1993. Some studies of molecularly imprinted membranes in combination with field effect devices. Sensors and Actuators 796: 37–38.

    Google Scholar 

  42. Mosbach, K. and Andersson, L.I. 1991. Förfarande för användning av molekylärt avtryckta polymerer som substratselektiv del i sensorer och mätapparater. Swedish Patent Application no. 9102843-1.

  43. Kriz, D., Ramström, O., Svensson, A. and Mosbach, K. 1995 Introducing biomimetic sensors based on molecularly imprinted polymers as recognition elements. Anal. Chem. 67: 2142–2144.

    CAS  Google Scholar 

  44. Andersson, L.I., O'Shannessy, D.J. and Mosbach, K. 1990. Molecular recognition in synthetic polymers. Preparation of chiral stationary phases by molecular imprinting of ammo acid amides, J. Chromatogr. 516: 167–179.

    Google Scholar 

  45. Kempe, M. and Mosbach, K. 1995. Receptor binding mimetics: a novel mol-ecularly imprinted polymer. Tetrahedron Lett. 36: 3563–3566.

    CAS  Google Scholar 

  46. Kempe, M. and Mosbach, K. 1991. Binding studies on substrate- and enan-tio-selective molecularly imprinted polymers. Anal. Lett. 24: 1137–1145.

    CAS  Google Scholar 

  47. O'Shannessy, D.J., Andersson, L.I. and Mosbach, K. 1989.Molecular recognition in synthetic polymers. Enantiomeric resolution of amide deriva-tives of amino acids on molecularly imprinted polymers. J. Mol. Recogn. 2(1): 1–5.

    Google Scholar 

  48. Sveç, F. and Fréchet, J.M. 1992. Continuous rods of macroporous polymer as high-performance liquid chromatography separation media. Anal. Chem. 64: 820–822.

    Google Scholar 

  49. Matsui, J., Kato, T., Takeuchi, T., Suzuki, M., Yokoyama, K., Tamiya, E. and Karube, I. 1993. Molecular recognition in continuous polymer rods prepared by a molecular imprinting technique. Anal. Chem. 65: 2223–2224.

    CAS  Google Scholar 

  50. Norrlöw, O., Glad, M. and Mosbach, K. 1984. Acrylic polymer preparations containing recognition sites obtained by imprinting with substrates. J. Chromatogr. 299: 29–41.

    Google Scholar 

  51. Glad, M., Reinholdsson, P. and Mosbach, K. 1995. Molecularly imprinted composite polymers based on trimethylolpropane trimethacrylate (TRIM) particles for efficient enantiomeric separations. Reactive Polymers 25: 47–54.

    CAS  Google Scholar 

  52. Dhal, P.K., Vidyasankar, S. and Arnold, F.H. 1995. Surface grafting of func-tional polymers to macroporous poly(trimethylolpropane trimethacrylate). Chem. Mater. 7(1): 154.

    CAS  Google Scholar 

  53. Byström, S.E., Börje, A. and Åkermark, B. 1993. Selective reduction of steroid 3- and 17-ketones using LiAlH4 activated template polymers. J. Am. Chem. Soc. 115: 2081–2083.

    Google Scholar 

  54. Hosoya, K., Yoshizako, K., Tanaka, N., Kimata, K., Araki, T. and Haginaka, J. 1994. Uniform-size macroporous polymer-based stationary phase for HPLC prepared through molecular imprinting technique. Chem. Lett., 1437–1438.

    Google Scholar 

  55. Sellergren, B. 1994. Imprinted dispersion polymers: a new class of easily accessible stationary phases. J. Chromatogr. A 673: 133–141.

    Google Scholar 

  56. Mayes, A. and Mosbach, K. 1995. Molecularly imprinted beads: suspension polymerisation using a liquid perfluorocarbon as the dispersing phase. Submitted

    Google Scholar 

  57. Norrlöw, O. 1986. Formation of substrate specific cavities in polymers by prearrangement of monomers prior to polymerization. Doctoral Thesis, University of Lund.

    Google Scholar 

  58. Norrlöw, O., Månsson, M.-O. and Mosbach, K. 1987. Improved chroma-tography: prearranged distances between boronate groups by the molecular imprinting approach. J. Chromatogr. 396: 374–377.

    Google Scholar 

  59. Dhal, P.K. and Arnold, F.H. 1992. Metal-coordination interactions in the template-mediated synthesis of substrate-selective polymers: Recognition of Bis(imidazole) substrates by Copper(II) iminodiacetate containing polymers. Macromolecules 25: 7051–7059.

    CAS  Google Scholar 

  60. Shnek, D.R., Pack, D.W., Sasaki, D.Y. and Arnold, F.H. 1994. Specific pro-tein attachments to artificial membranes via coordination to lipid-bound copper(II). Langmuir 10: 2382–2388.

    CAS  Google Scholar 

  61. Morihara, K., Takiguchi, M. and Shimada, T. 1994. Footprint catalysis. XI. Molecular footprint cavities imprinted with chiral amines and their chiral molecular recognition. Bull. Chem. Soc. Jpn. 67: 1078–1084.

    Google Scholar 

  62. Tahmassebi, D.C. and Sasaki, T. 1994. Synthesis of a new trialdehyde tem-plate for molecular imprinting. J. Org. Chem. 59: 579–681.

    Google Scholar 

  63. Kempe, M., Glad, M. and Mosbach, K. 1995. An approach towards surface imprinting using the enzyme ribonuclease A. J. Mol. Recogn. 8: 35–39.

    CAS  Google Scholar 

  64. Tsukagoshi, K., Yu, K.Y., Maeda, M. and Takagi, M. 1993. Metal ion-selec-tive adsorbent prepared by surface-imprinting procedure. Bull. Chem. Soc. Jpn. 66: 114–120.

    CAS  Google Scholar 

  65. Andersson, L., Sellergren, B. and Mosbach, K. 1984. Imprinting of amino acid derivatives in macroporous polymers. Tetrahedron Lett. 25: 5211–5214.

    CAS  Google Scholar 

  66. Sellergren, B., Lepistö, M. and Mosbach, K. 1988. Highly enantioselective and substrate-selective polymers obtained by molecular imprinting utilizing non-covalent interactions. NMR and chromatographic studies on the nature of recognition. J. Am. Chem. Soc. 110: 5853–5860.

    Google Scholar 

  67. Kempe, M., Fischer, L. and Mosbach, K. 1993. Chiral separation using mol-ecularly imprinted heteroaromatic polymers. J. Mol. Recogn. 6: 25–29.

    CAS  Google Scholar 

  68. Wulff, G., Kemmerer, R., Vietmeier, J. and Poll, H. H.1982. Chirality of Vinyl Polymers. The Preparation of Chiral Cavities in Synthetic Polymers. Nouv. J. Chim. 6(12): 681–687.

    Google Scholar 

  69. Glad, M., Norrlöw, O., Sellergren, B., Siegbahn, N. and Mosbach, K. 1985. Use of silane monomers for molecular imprinting and enzyme entrapment in polysiloxane-coated porous silica. J. Chromatogr. 347: 11–23.

    CAS  Google Scholar 

  70. Venton, D.L. and Gudipati, E. 1995. Influence of protein on polysiloxane polymer formation: evidence for induction of complementary protein-poly-mer interactions. Biochim. Biophys. Acta 1250: 126–136.

    PubMed  Google Scholar 

  71. Ståhl, M., Jeppsson-Wistrand, U., Månsson, M.-O. and Mosbach, K. 1991. Induced stereoselectivity and substrate selectivity of bio-imprinted α-chymotrypsin in anhydrous organic media. J. Am. Chem. Soc. 113: 9366–9368.

    Google Scholar 

  72. Johansson, A., Mosbach, K. and Månsson, M.-O. 1995. Horse liver alcohol dehydrogenase can accept NADP+ as coenzyme in high concentrations of ace-tonitrile. Eur. J. Biochem. 227: 551–555.

    CAS  PubMed  Google Scholar 

  73. Dabulis, K. and Klibanov, A.M. 1992. Molecular imprinting of proteins and other macromolecules resulting in new adsorbents. Biotech. Bioeng. 39: 176–185.

    CAS  Google Scholar 

  74. Siemann, M., Andersson, L.I. and Mosbach, K. 1995. Selective recognition of the herbizide atrazine by non-covalent molecularly imprinted polymers. J. Agric. Food Chem. In press.

  75. Muldoon, M.T. and Stanker, L.H. 1995. Polymer synthesis and characterization of a molecularly imprinted sorbent assay for atrazine. J. Agric. Food Chem. 43: 1424–1427.

    CAS  Google Scholar 

  76. Matsui, J., Doblhoffdier, O. and Takeuchi, T. 1995. Atrazine-selective poly-mer prepared by molecular imprinting technique. Chem. Lett. 6: 489.

    Google Scholar 

  77. Sellergren, B. 1994. Imprinted dispersion polymers: a new class of easily accessible affinity stationary phases. J. Chromatogr. 673: 133–141.

    CAS  Google Scholar 

  78. Kempe, M. and Mosbach, K. 1995. Molecular separations used for chiral sep-arations. J. Chromatogr. 694: 3–13.

    CAS  Google Scholar 

  79. Kempe, M. and Mosbach, K. 1995. Novel molecularly imprinted polymers showing unusually high resolution and load capacity. Submitted.

    Google Scholar 

  80. Nilsson, K.G.I., Sakaguchi, K., Gemeiner, P. and Mosbach, K. 1995. Molec-ular imprinting of acetylated carbohydrate derivatives into methacrylic poly-mers. J. Chromatogr. 707: 199–203.

    CAS  Google Scholar 

  81. Mayes, A.G., Andersson, L.I. and Mosbach, K. 1994. Sugar binding poly-mers showing high anomeric and epimeric discrimination by non-covalent molecular imprinting. Anal. Biochem. 222: 483–488.

    CAS  PubMed  Google Scholar 

  82. Wulff, G. and Haarer, J. 1991. Enzyme-analogue built polymers. The prepa-ration of defined chiral cavities for the racemic resolution of free sugars. Makromol. Chem. 192: 1329–1338.

    Google Scholar 

  83. Wulff, G., Oberkobusch, D. and Minarik, M. 1985. Enzyme-analogue built polymers. Chiral cavities in polymer layers coated on wide-pore silica. Reactive Polymers 3: 261–275.

    Google Scholar 

  84. Shea, K.J., Spivak, D.A. and Sellergren, B. 1993. Polymer complements to nucleotide bases. Selective binding of adenine derivatives to imprinted poly-mers. J. Am. Chem. Soc. 115: 3368–3369.

    Google Scholar 

  85. Sarhan, A. and El-Zahab, M.A. 1987. Racemic resolution of mandelic acid on polymers with chiral cavities, 2. Enzyme-analogue stereospecific conversion of configuration. Makromol. Chem., Rapid Commun. 8: 555–561.

    Google Scholar 

  86. Rosatzin, T., Andersson, L.I., Simon, W. and Mosbach, K. 1990. Preparation of Ca2+ selective sorbents by molecular imprinting using polymerisable ionophores. J. Chem. Soc., Perkin Trans. 2: 1261–1265.

    Google Scholar 

  87. Kuchen, W. and Schram, J. 1988. Metal-ion selective exchange resins by matrix imprint with methacrylates. Angew. Chem. Int. Ed. Engl. 27: 1695–1697.

    Google Scholar 

  88. Andersson, L.I., Ekberg, B. and Mosbach, K. 1993. Bioseparation and catalysis in molecularly imprinted polymers, p. 383–395. In: Molecular Interactions in Bioseparations, Ngo, T. T. (Ed.). New York, Plenum Press.

    Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Rights and permissions

Reprints and permissions

About this article

Cite this article

Mosbach, K., Ramström, O. The Emerging Technique of Molecular Imprinting and Its Future Impact on Biotechnology. Nat Biotechnol 14, 163–170 (1996). https://doi.org/10.1038/nbt0296-163

Download citation

  • Issue Date:

  • DOI: https://doi.org/10.1038/nbt0296-163

This article is cited by

Search

Quick links

Nature Briefing

Sign up for the Nature Briefing newsletter — what matters in science, free to your inbox daily.

Get the most important science stories of the day, free in your inbox. Sign up for Nature Briefing