Probe Sonication

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Probe Sonication

  1. 1. Probe Sonication Why Probe Sonication? What are It’s Uses?
  2. 2. Introduction <ul><li>My name is Vaughn Audain </li></ul>
  3. 3. Can we do this more efficiently? <ul><li>During the early stages of the development of Combinatorial ADME Screens </li></ul><ul><li>There were several key needs-processes identified </li></ul><ul><li>Reason? </li></ul>
  4. 4. Drug Discovery Process <ul><li>Took ~10-15 years from candidate selection until a new medicine was launched </li></ul><ul><li>Can this be reduced to ~7-10 years? </li></ul>
  5. 5. How can this be accomplished? <ul><li>Increase throughput </li></ul><ul><li>Automate </li></ul><ul><li>Make Key decisions Quickly </li></ul><ul><li>Develop Traffic lights to aid the decision making process </li></ul>
  6. 6. My Process: Solubility determination <ul><li>Old process : </li></ul><ul><li>Equilibrium Solubility </li></ul><ul><li>This took up to 30days per compound (several time points) with a need for more drug substance for this large scale process </li></ul><ul><li>Therefore due to this limitation; decisions made later </li></ul>
  7. 7. New Process: <ul><li>Allowed quicker progression support (Approximately 400 samples per day) </li></ul><ul><li>Developed and assayed with a 2.5 minutes HPLC reverse phase method </li></ul><ul><li>Liquid stored compounds in 96 well plates. Allowed quicker distribution to project teams and faster sample preparation (Kinetic solubility) </li></ul>
  8. 8. Challenges <ul><li>Need for DMSO evaporation for more accurate solubility determination </li></ul><ul><li>Encountered Problems with adhesion on the bottom of the well plates </li></ul><ul><li>Hence the Probe Sonicator </li></ul><ul><li>Facilitate dissolution </li></ul>
  9. 9. Probe requirements for efficiency-automation <ul><li>Adjustable energy source </li></ul><ul><li>Size (fit vials,well plates etal) </li></ul><ul><li>Liquid handling capabilities </li></ul><ul><li>Low-zero dead volume </li></ul><ul><li>Conductivity sensor for liquid level detection </li></ul><ul><li>Robotics (X,Y,Z) Control </li></ul><ul><li>Durability and low carry over </li></ul>
  10. 10. Probe Capabilities <ul><li>(57)  A hollow probe cooperates with an ultrasonic transducing device designed with liquid flow-through capability. The probe and transducing device are combined into a probe assembly, which can be integrated into an automated liquid handling workstation. As a functional component of the workstation, the probe can be connected to and manipulated by a robotic arm of the workstation, and thus programmed to move in three-dimensional space to and from various locations of the sampling apparatus. In particular, the probe can be inserted into the individual wells or test tubes of a plate or rack utilized to contain sample substances. The probe can be used to conduct a variety of liquid handling tasks and additionally can be used to ultrasonically excite sample substances contained in the individual wells of the plate, thereby improving dilution of such sample substances and increasing throughput of any given sample preparation procedure. A liquid level detection device can be connected to the probe assembly. </li></ul>
  11. 11. Probe Sonicator Uses <ul><li>Have been used for: </li></ul><ul><li>Tissue </li></ul><ul><li>Solids (i.e. drug substance) </li></ul><ul><li>Dissolution of glassy polymorphs </li></ul><ul><li>Packing columns </li></ul>
  12. 12. Value to Discovery <ul><li>Shorter Cycle time for drug development </li></ul><ul><li>Reduction of failures: Note compound shortfalls earlier (Toxicity,Absorption,Permeability,Metabolism,Stability) </li></ul><ul><li>Several ADME screens developed and assayed in parallel </li></ul><ul><li>Hence Lower Cost (Time=Money) </li></ul>
  13. 13. Screens Launched <ul><li>All screens launched worldwide </li></ul><ul><li>Received RAVE Award (Rewarding and Acknowledging Valuable Employees) </li></ul><ul><li>Software developed to make system Open Access </li></ul>
  14. 14. Patent : ULTRASONIC TRANSDUCING PROBE WITH LIQUID FLOW-THROUGH CAPABILITY AND RELATED AUTOMATED WORKSTATION AND METHODS OF USING SAME <ul><li>AUDAIN, Vaughn, A. ; BUCKNER, Charles ; ORMAND, James, R. [US/US]; GlaxoSmithKline, Five Moore Drive, P.O. Box 13398, Research Triangle Park, NC 27709 (US). GEYSEN, Hendrick, Mario [AU/US]; University of Virginia, McCormick Road, Charlottesville, VA 22904 (US). </li></ul><ul><li>LEVY, David, J., et al ; GlaxoSmithKline, Five Moore Drive, P.O. Box 13398, Research Triangle Park, NC 27709 (US). </li></ul><ul><li>Patent # WO 02/ 079751 , PCT/US01/44451 </li></ul>
  15. 15. Acknowlegement <ul><li>GlaxoSmithkline Inc. </li></ul><ul><li>Misonex </li></ul>

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