Skip to main content
SpringerLink
Log in

Designed protein binders in combination with nanocrystalline diamond for use in high-sensitivity biosensors

  • Original Paper
  • Published:
Analytical and Bioanalytical Chemistry Aims and scope Submit manuscript

Abstract

A platform for diagnostic applications showing signal-to-noise ratios that by far surpass those of traditional bioanalytical test formats has been developed. It combines the properties of modified nanocrystalline diamond (NCD) surfaces and those of polyethylene oxide and polypropylene oxide based block copolymers for surface passivation and binder conjugation with a new class of synthetic binders for proteins. The NCD surfaces were fluorine-, hydrogen-, or oxygen-terminated prior to further biofunctionalization and the surface composition was characterized by X-ray photoelectron spectroscopy. In a proof of principle demonstration targeting the C-reactive protein, an ELISA carried out using an F-terminated diamond surface showed a signal-to-noise ratio of 3,900 which compares well to the signal-to-noise of 89 obtained in an antibody-based ELISA on a polystyrene microtiter plate, a standard test format used in most life science laboratories today. The increase in signal-to-noise ratio is to a large extent the result of extremely efficient passivation of the diamond surface. The results suggest that significant improvements can be obtained in standardized test formats using new materials in combination with new types of chemical coatings and receptor molecules.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3

Similar content being viewed by others

References

  1. Härtl A, Schmich E, Garrido JA, Hernando J, Catharino SCR, Walter S, Feulner P, Kromka A, Steinmüller D, Stutzmann M (2004) Protein-modified nanocrystalline diamond thin films for biosensor applications. Nat Mater 3:736–742

    Article  Google Scholar 

  2. Baltzer L (2012) Crossing borders to bind proteins—a new concept in protein recognition based on the conjugation of small organic molecules or short peptides to polypeptides from a designed set. Anal Bioanal Chem 400(6):1653–1664

    Article  Google Scholar 

  3. Rifai N, Ridker PM (2001) High-sensitivity C-reactive protein: a novel and promising marker of coronary heart disease. Clin Chem 47:403–411

    CAS  Google Scholar 

  4. Pepys MB, Hirschfield GM (2003) C-reactive protein: a critical update. J Clin Invest 111:1805–1812

    CAS  Google Scholar 

  5. Tegler LT, Nonglaton G, Büttner F, Caldwell K, Christopeit T, Danielsson H, Fromell K, Gossas T, Larsson A, Longati P, Norberg T, Ramapanicker R, Rydberg J, Baltzer L (2011) Efficient protein binders for the C-reactive protein from a designed chemically modified peptide library—a new concept for biomolecular recognition. Angew Chem 50:1823–1827

    Article  CAS  Google Scholar 

  6. Li JT, Carlsson J, Lin JN, Caldwell KD (1996) Chemical modification of surface active poly(ethylene oxide)-poly(propylene oxide) triblock copolymers. Bioconj Chem 7:592–599

    Article  CAS  Google Scholar 

  7. Vivensang C, Turban G, Anger E, Giquel A (1994) Reactive ion etching of diamond and diamond-like carbon films. Diam Relat Mater 3:645–649

    Article  CAS  Google Scholar 

  8. Shirafuji J, Sakamoto Y, Furukawa A, Shigeta H, Sugino T (1995) X-ray photoelectron spectroscopy analysis of plasma-treated surfaces of diamond films. Diam Relat Mater 4:984–988

    Article  CAS  Google Scholar 

  9. Maier F, Graupner R, Hollering M, Hammer L, Ristein J, Ley L (1999) The hydrogenated and bare diamond (110) surface: a combined LEED-, XPS-, and ARPES study. Surf Sci 443:177–185

    Article  CAS  Google Scholar 

  10. Francz G, Reinke P, Oelhafen P, Hänni W (1995) Photoelectron spectroscopy of ion-irradiated B-doped CVD diamond surfaces. Thin Solid Films 270:200–204

    Article  CAS  Google Scholar 

  11. Steinmüller-Nethl D, Kloss FR, Najam-Ul-Haq M, Rainer M, Larsson K, Linsmeier C, Köhler G, Gassner R, Fehrer C, Lepperdinger G, Huck CW, Bonn G (2006) Strong physisorption of BMP-2 on nanocrystalline diamond retains bioactivity. Biomaterials 27:4547–4556

    Article  Google Scholar 

  12. Petrini D, Larsson K (2007) A theoretical approach to the energetic stability and geometry of hydrogen and oxygen terminated diamond (100) surfaces. J Phys Chem C 111:795

    Article  CAS  Google Scholar 

  13. Christopeit T, Gossas T, Danielson UH (2009) Characterization of Ca2+ and phosphocholine interactions with C-reactive protein using a surface plasmon resonance biosensor. Anal Biochem 391:39–44

    Article  CAS  Google Scholar 

  14. Neff JA, Caldwell KD, Tresco PA (1998) A novel method for surface modification to promote cell attachment to hydrophobic substrates. J Biomed Mater Res 40:511–519

    Article  CAS  Google Scholar 

  15. Karlsson M, Forsberg P, Nikolajeff F (2010) From hydrophilic to superhydrophobic: fabrication of micrometer-sized nail-head-shaped pillars in diamond. Langmuir 26:889–892

    Article  CAS  Google Scholar 

  16. ter Veen R, Fromell K, Caldwell KD (2005) Shifts in polystyrene particle surface charge upon adsorption of the Pluronic F108 surfactant. J Colloids Interface Sci 288:124–128

    Article  Google Scholar 

  17. Albrecht C, Fechner P, Honcharenko D, Baltzer L, Gauglitz G (2010) A new assay design for clinical diagnostics based on alternative recognition elements. Biosens Bioelectron 25:2302–2308

    Article  CAS  Google Scholar 

Download references

Acknowledgments

This work has enjoyed financial support from the Uppsala Berzelii Technology Centre for Neurodiagnostics and by The Swedish Diamond Centre. We also wish to thank Allvivo Inc. for supporting us with Pluronic F108-PDS.

Author information

Authors and Affiliations

  1. Department of Biochemistry and Organic Chemistry, Uppsala University, P.O. Box 576, 751 23, Uppsala, Sweden

    Karin Fromell & Lars Baltzer

  2. Department of Engineering Sciences, Uppsala University, P.O. Box 534, 751 21, Uppsala, Sweden

    Pontus Forsberg, Mikael Karlsson & Fredrik Nikolajeff

  3. Department of Materials Chemistry, Uppsala University, P.O. Box 538, 751 21, Uppsala, Sweden

    Karin Larsson

Authors
  1. Karin Fromell
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Pontus Forsberg
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Mikael Karlsson
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Karin Larsson
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Fredrik Nikolajeff
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Lars Baltzer
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Karin Fromell.

Electronic supplementary material

Below is the link to the electronic supplementary material.

ESM 1

(PDF 69 kb)

Rights and permissions

Reprints and permissions

About this article

Cite this article

Fromell, K., Forsberg, P., Karlsson, M. et al. Designed protein binders in combination with nanocrystalline diamond for use in high-sensitivity biosensors. Anal Bioanal Chem 404, 1643–1651 (2012). https://doi.org/10.1007/s00216-012-6245-7

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00216-012-6245-7

Keywords

Search

Navigation