Research Abstract

Research Abstract

Our work focuses on the development of simple, convenient bio-sensor probes for the quantitative, rapid detection of proteins and other bio-molecules. These probes comprise a versatile new class of oligonucleotide-based “switches” that recognize proteins using native binding interactions. This approach simplifies the rational design of sensors directed to bind any target of interest and allows the sensors to have affinity and specificity on the order of natural binding interactions. This design has been put into practice with beacons directed against diverse human transcription factors, biological toxins, and other proteins. For all targets we find rapid (minutes), specific quantification of nanomolar concentrations, retaining selectivity even in media as complex as blood. These bio-sensors represent a convenient, versatile, and readily generalized approach to detect proteins and other bio-molecules that provides significant advantages over existing methods.

1. Stephen R. Schaffner, Kathryn Norquest, Elina Baravik, Jody Stephens, Lisa Fetter, Ryan M. Masterson, Yerelsy Reyna, Andrew J. Bonham. Conformational design optimization of transcription factor beacon DNA biosensors. Sensing & BioSensing Research, 2014, 2, p 49. doi: 10.1016/j.sbsr.2014.10.007

2. Ferguson, B. Scott, Hoggarth, David A., Maliniak, Dan, Ploense, Kyle, White, Ryan J., Woodward, Nick, Hsieh, Kuangwen, Bonham, Andrew J., Eisenstein, Michael, Kippin, Tod, Plaxco, Kevin W., Soh, H. Tom.
Real-time, aptamer-based tracking of circulating therapeutic agents in living animals. Science Translational Medicine, 2013, 5(213), p 165. doi: 10.1126/scitranslmed.3007095

3. Andrew J. Bonham, Nicole G. Padman, Francesco Ricci, and Kevin W. Plaxco.
Detection of IP-10 protein marker in undiluted blood serum via an electrochemical E-DNA scaffold sensor. Analyst, 2013,138(19), p 5580-5583, doi: 10.1039/c3an01079a

4. Andrew J. Bonham, Leah M. Osslund, Aaron J. Prussin II, Nikola Wenta, Uwe Vinkemeier, and Norbert O. Reich.
STAT1 DNA-sequence dependent binding specificity modulation by phosphorylation, protein:protein interactions, and small molecules. Nuc. Acids Res., 2012, doi: 10.1093/nar/gks1085

5. Andrew J. Bonham, Kuangwen Hsieh, B. Scott Ferguson, Alexis Vallée-Bélisle, Francesco Ricci, H. Tom Soh, and Kevin W. Plaxco. Quantification of Transcription Factor Binding in Cell Extracts Using an Electrochemical, Structure-Switching Biosensor. J. Am. Chem. Soc., 2012, 134 (7), 3346–3348. doi:10.1021/ja2115663

6. Andrew J. Bonham, Alexis Vallée-Bélisle, Norbert O. Reich, Francesco Ricci, and Kevin W. Plaxco. Transcription Factor Beacons for the Quantitative Detection of DNA Binding Activity. J. Am. Chem. Soc., 2011, 133 (35), 13836–13839. doi:10.1021/ja204775k

7. Aaron A Rowe, Andrew J Bonham, Ryan J White, Michael P Zimmer, Ramsin J Yadgar, Tony M Hobza, Jim Honea, Ilan Ben-Yaacov, Kevin W Plaxco. CheapStat: an open-source, “do-it-yourself” potentiostat for analytical and educational applications. PLoS ONE, Sep 13, 2011, doi:10.1371/journal.pone.0023783

8. Aaron A Rowe, Ryan J White, Andrew J Bonham, Kevin W Plaxco. Fabrication of Electrochemical-DNA Biosensors for the Reagentless Detection of Nucleic Acids, Proteins and Small Molecules. Journal of Visualized Experiments, 2011, 52, doi:10.3791/2922

9. Andrew J. Bonham. Novel optical techniques for exploring the DNA binding affinity and specificity of eukaryotic transcription factors and transcription factor complexes. Dissertation, March 2010, open access:

10. Thorsten Neumann, Andrew J. Bonham, Gregory Dame, Bernd Berchtold, Oswald Prucker, Norbert O. Reich, and Juergen Ruehe. Temperature and time resolved TIRF analysis of reusable DNA hydrogel chips. Anal. Chem., 2010, 82(14), 6124-6131, doi:10.1021/ac1008578

11. Andrew J. Bonham, Thorsten Neumann, Matthew Tirrell, and Norbert O. Reich. Tracking transcription factor complexes on DNA using total internal reflectance fluorescence protein binding microarrays. Nuc. Acids Res., 2009, 37(13), e94, doi:10.1093/nar/gkp424

12. Francesco Ricci, Andrew J. Bonham, Aaron C. Mason, Norbert O. Reich, and Kevin W. Plaxco. Reagentless, Electrochemical Approach for the Specific Detection of Double- and Single-Stranded DNA Binding Proteins. Anal. Chem., 2009, 81 (4), p 1608–1614, doi:10.1021/ac802365x

13. Andrew J. Bonham, Gary Braun, Ioana Pavel, Martin Moskovits, and Norbert O. Reich. Detection of Sequence-Specific Protein-DNA Interactions via Surface Enhanced Resonance Raman Scattering. J. Amer. Chem. Soc., 2007, 129 (47), p 14572–14573, doi:10.1021/ja0767837

14. Teisha Jane Rowland, Liane M Miller, Alison J Blaschke, E. Lauren Doss, Andrew J. Bonham, Sherry T Hikita, Lincoln V Johnson, Dennis O Clegg. Roles of Integrins in Human Induced Pluripotent Stem Cell Growth on Matrigel and Vitronectin. Stem Cells and Development. doi:10.1089/scd.2009.0328

Return to top of page