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Séminaire Chimie ED459

An ultra-sensitive, low-volume, free-solution, label-free chemical sensing platform

Prof. Darryl J. Bornhop (Vanderbilt Institute for Chemical Biology, and Vanderbilt Ingram Cancer Center ; Vanderbilt University and Vanderbilt University Medical Center, Nashville TN, USA)

publié le

Le Jeudi 24 Octobre 2013 à 13h45
UM2, salle de cours SC-16.01

Back-scattering interferometry (BSI) is a universal sensing platform with ultrahigh sensitivity (zeptomole) and picoliter detection volumes. It has a simple optical train, consisting of a coherent source, microfluidic chip and detector. This overview presentation will teach how BSI works and show it is a tool that can be widely used across scientific disciplines. For example it will be shown that a unique multi-pass configuration allows BSI to transduce minute changes in the refractive index of a solution into equilibrium binding constants over a range of at least six orders of magnitude,[1,2] without any labeling and in free-solution. Quantification at the level of femtomolar concentrations in complex milieu will be demonstrated, as will the quantification of binding affinity for antibody-antigen,[2] protein-ion, protein-protein, and aptamer-protein-aptamer interactions.[3] Respiratory virus RNA detection investigations will illustrate that BSI measures conformational changes and can be a quite sensitive detector.[4] Then, DNA hybridization determinations and sugar-lectin binding studies[5] will illustrate that BSI is not limited by mass sensitivity as with other ‘bio’-sensors, and lends insights into multivalent interactions, while quantifying the influence of labels and/or surface immobilization. Next, direct quantification of binding affinities for membrane-associated protein drug targets in native bilayer environments[6] will show BSI has allowed characterization molecular mechanism studies[7] and the quantification of allosteric binding in CXCR-4.[8] Finally, work on hydrogen bonding studies in non-aqueous media[8] will show more general applicability of BSI, while investigations toward near-patient diagnostics and biomarker validation provides evidence it is a quantitative sensor with significant advantages in biomarker validation.


1. Free-Solution, Label-Free Molecular Interactions Studied by Back-scattering Interferometry. D.J. Bornhop, J.C. Latham, A. Kussrow, D.A. Markov, R.D. Jones, and H.S. Sørensen, Science, Sept. 21 ; 317(5845) : 1732-1736, (2007).
2. Universal Sensing by Transduction of Antibody Binding using Backscattering Interferometry. A. Kussrow, M. M. Baksh, D.J. Bornhop, M.G. Finn, ChemBioChem, 12(3) : 367-70 (2011).
3. Measurement of Aptamer-Protein Interactions with Back-scattering Interferometry. I.R. Olmsted, Y. Xiao, M. Cho, A. Csordas, J.H. Sheehan, J. Meiler, H.T. Soh, D.J. Bornhop, Analytical Chemistry, 83(23) : 8867-70 (2011).
4. The effect of hybridization-induced secondary structure alterations on RNA detection using backscattering interferometry, N. Adams, I. Olmsted, F. Haselton, D.J. Bornhop, D. Wright, Nucleic Acids Research, 41(9) : e103 (2013).
5. Comparison of Free-solution and Surface-immobilized Molecular Interactions using a Single Platform, Backscattering Interferometry. I. R. Olmsted, A. Kussrow, and D. J. Bornhop, Analytical Chemistry, 84(24) : 10817-22 (2012).
6. Quantitation of Membrane-Ligand Interactions Using Backscattering Interferometry. M.M. Baksh, A. Kussrow, M. Mileni, M.G. Finn, D. J. Bornhop, Nature Biotechnology, 29(4) : 357-60 (2011). (The Economist, June 4-10, 2011)
7. Baclofen and other GABAB receptor agents are allosteric modulators of the CXCL12 chemokine receptor CXCR4. A. Guyon, A. Kussrow, I. Olmsted, D. J. Bornhop and J-L. Nahon, Journal of Neuroscience, July 10 ; 33(28) : 11643-11654 (2013). PMID : 23843532
8. Study of Hydrogen Binding Interactions in Acetonitrile using Back-scattering Interferometry. E.N. Presciotta, D.J. Bornhop, R.A. Flowers, Organic Letters, 13(10) : 2654-7 (2011).

Contact local IBMM : Prof. Hervé Cottet (équipe DSBC)


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