Multifunctional Nanoparticles As Simulants for a Gravimetric Immunoassay

Overview

Journal Anal Bioanal Chem

Specialty Chemistry

Date 2010 Nov 27

PMID 21110011

Citations 6

Authors

Scott A Miller

Leslie A Hiatt

Robert G Keil

David W Wright

David E Cliffel

Affiliations

Soon will be listed here.

Abstract

Immunoassays are important tools for the rapid detection and identification of pathogens, both clinically and in the research laboratory. An immunoassay with the potential for the detection of influenza was developed and tested using hemagglutinin (HA), a commonly studied glycoprotein found on the surface of influenza virions. Gold nanoparticles were synthesized, which present multiple peptide epitopes, including the HA epitope, in order to increase the gravimetric response achieved with the use of a QCM immunosensor for influenza. Specifically, epitopes associated with HA and FLAG peptides were affixed to gold nanoparticles by a six-mer PEG spacer between the epitope and the terminal cysteine. The PEG spacer was shown to enhance the probability for interaction with antibodies by increasing the distance the epitope extends from the gold surface. These nanoparticles were characterized using thermogravimetric analysis, transmission electron microscopy, matrix-assisted laser desorption/ionization-time of flight, and (1)H nuclear magnetic resonance analysis. Anti-FLAG and anti-HA antibodies were adhered to the surface of a QCM, and the response of each antibody upon exposure to HA, FLAG, and dual functionalized nanoparticles was compared with binding of Au-tiopronin nanoparticles and H5 HA proteins from influenza virus (H5N1). Results demonstrate that the immunoassay was capable of differentiating between nanoparticles presenting orthogonal epitopes in real-time with minimal nonspecific binding. The detection of H5 HA protein demonstrates the logical extension of using these nanoparticle mimics as a safe positive control in the detection of influenza, making this a vital step in improving influenza detection methodology.

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References

Harkness K, Fenn L, Cliffel D, McLean J . Surface fragmentation of complexes from thiolate protected gold nanoparticles by ion mobility-mass spectrometry. Anal Chem. 2010; 82(7):3061-6. PMC: 2848286. DOI: 10.1021/ac100251d. View

Tang D, Yuan R, Chai Y, Zhong X, Liu Y, Dai J . Novel potentiometric immunosensor for hepatitis B surface antigen using a gold nanoparticle-based biomolecular immobilization method. Anal Biochem. 2004; 333(2):345-50. DOI: 10.1016/j.ab.2004.06.035. View

Jadzinsky P, Calero G, Ackerson C, Bushnell D, Kornberg R . Structure of a thiol monolayer-protected gold nanoparticle at 1.1 A resolution. Science. 2007; 318(5849):430-3. DOI: 10.1126/science.1148624. View

Wittenberg N, Haynes C . Using nanoparticles to push the limits of detection. Wiley Interdiscip Rev Nanomed Nanobiotechnol. 2010; 1(2):237-54. DOI: 10.1002/wnan.19. View

Agasti S, Rana S, Park M, Kim C, You C, Rotello V . Nanoparticles for detection and diagnosis. Adv Drug Deliv Rev. 2009; 62(3):316-28. PMC: 2827652. DOI: 10.1016/j.addr.2009.11.004. View

Peduru Hewa T, Tannock G, Mainwaring D, Harrison S, Fecondo J . The detection of influenza A and B viruses in clinical specimens using a quartz crystal microbalance. J Virol Methods. 2009; 162(1-2):14-21. PMC: 7112868. DOI: 10.1016/j.jviromet.2009.07.001. View

Yang L, Biswas M, Chen P . Study of binding between protein A and immunoglobulin G using a surface tension probe. Biophys J. 2003; 84(1):509-22. PMC: 1302631. DOI: 10.1016/S0006-3495(03)74870-X. View

Muller G, Shapira M, Arnon R . Anti-influenza response achieved by immunization with a synthetic conjugate. Proc Natl Acad Sci U S A. 1982; 79(2):569-73. PMC: 345786. DOI: 10.1073/pnas.79.2.569. View

Van Regenmortel M . The concept and operational definition of protein epitopes. Philos Trans R Soc Lond B Biol Sci. 1989; 323(1217):451-66. DOI: 10.1098/rstb.1989.0023. View

10.

Bowman M, Ballard T, Ackerson C, Feldheim D, Margolis D, Melander C . Inhibition of HIV fusion with multivalent gold nanoparticles. J Am Chem Soc. 2008; 130(22):6896-7. PMC: 2916654. DOI: 10.1021/ja710321g. View

11.

Wilson I, Niman H, Houghten R, Cherenson A, Connolly M, Lerner R . The structure of an antigenic determinant in a protein. Cell. 1984; 37(3):767-78. DOI: 10.1016/0092-8674(84)90412-4. View

12.

Mackiewicz M, Hodges H, Reed S . C-reactive protein induced rearrangement of phosphatidylcholine on nanoparticle mimics of lipoprotein particles. J Phys Chem B. 2010; 114(16):5556-62. PMC: 2930195. DOI: 10.1021/jp911617q. View

13.

Lu Y, Ding J, Liu W, Chen Y . A candidate vaccine against influenza virus intensively improved the immunogenicity of a neutralizing epitope. Int Arch Allergy Immunol. 2002; 127(3):245-50. DOI: 10.1159/000053869. View

14.

Ho K, Tsai P, Lin Y, Chen Y . Using biofunctionalized nanoparticles to probe pathogenic bacteria. Anal Chem. 2004; 76(24):7162-8. DOI: 10.1021/ac048688b. View

15.

Montet X, Funovics M, Montet-Abou K, Weissleder R, Josephson L . Multivalent effects of RGD peptides obtained by nanoparticle display. J Med Chem. 2006; 49(20):6087-93. DOI: 10.1021/jm060515m. View

16.

Wegner G, Lee H, Corn R . Characterization and optimization of peptide arrays for the study of epitope-antibody interactions using surface plasmon resonance imaging. Anal Chem. 2002; 74(20):5161-8. DOI: 10.1021/ac025922u. View

17.

Mani V, Chikkaveeraiah B, Patel V, Gutkind J, Rusling J . Ultrasensitive immunosensor for cancer biomarker proteins using gold nanoparticle film electrodes and multienzyme-particle amplification. ACS Nano. 2009; 3(3):585-94. PMC: 2666939. DOI: 10.1021/nn800863w. View

18.

Hirst E, Yuan Y, Xu W, Bronlund J . Bond-rupture immunosensors--a review. Biosens Bioelectron. 2008; 23(12):1759-68. DOI: 10.1016/j.bios.2008.02.002. View

19.

Gerdon A, Wright D, Cliffel D . Quartz crystal microbalance detection of glutathione-protected nanoclusters using antibody recognition. Anal Chem. 2004; 77(1):304-10. DOI: 10.1021/ac048953t. View

20.

Sardar R, Funston A, Mulvaney P, Murray R . Gold nanoparticles: past, present, and future. Langmuir. 2009; 25(24):13840-51. DOI: 10.1021/la9019475. View