Séminaires & Conférences Chimie École Doctorale 459
Salle de Cours SC-16.01 – Université Montpellier II An ultra-sensitive, low-volume, free-solution, label-free chemical sensing platform
Prof. Darryl J. BORNHOP Department of Chemistry, The Vanderbilt Institute for Chemical Biology, and Vanderbilt Ingram Cancer
Center; Vanderbilt University and Vanderbilt University Medical Center, Nashville TN, 37235
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.
References 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).
GUIDELINES FOR INPATIENT DIABETES MANAGEMENT These recommendations do not take into account individual patient situations, and do not substitute for clinical judgment. Changes in diet, activity, medications (i.e.: steroids), and acuity of illness (i.e.: infection, renal insufficiency) may quickly change treatment requirements Inpatient Blood Glucose Targets: 80-180mg/dL (In the ICU s
Curriculum Professionale ------------------------------------------------------------------------------------------------------------------------ Luogo e data di nascita: Roma, 06/07/1975 ------------------------------------------------------------------------------------------------------------------------ Luglio 2002 . Laurea in Medicina e Chirurgia presso L’Università degli Studi d