Notes
Slide Show
Outline
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"Centrifugation Based Automated Synthesis Technologies"
  • Centrifugation Based Automated Synthesis Technologies
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"Centrifugation:"
  • Centrifugation:
  • The Only Technique
  •  for
  • Massively Parallel Solid Phase Synthesis
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Filtration is Dead!
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Solid Phase Synthesis
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Solid Phase Synthesis
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It All Started With…
  • Jouan….
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Or Did It All Start With…
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Or Did It All Start With…
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Actually It All Started With…
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It All Started With Cotton
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Centrifugal (Cotton) Veterans
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CSPS
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Continual Solid Phase Synthesis (CSPS)
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Concept of Centrifugal Synthesizer
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The First “Compas”
 
(Cotton Multiple Peptide Synthesizer)
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Spyder Instruments
  • Started in 1992 in San Diego
  • The first product - Compas 242
    • multiple automatic peptide synthesizer
      • centrifugation
      • inclusion volume coupling
    • US Patents 5,202,418, 5,338,831, 5,342,585
  • SBIR Phase I and II grant recipient
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Compas 242
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Tilted Centrifugation
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Tilted Centrifugation
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Studying Cross-Contamination Issue
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Single Bead in a Well
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No Cross Contamination
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Microplate CFD Results
  • Zero cross contamination
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Crude Model and First Prototype
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Second Generation Compas 768
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Synthesis Algorithm
  • Distribute resin (5 mg/well) into microtiterplates
    • multichannel pipetting
  • Place plates into COMPAS
  • Distribute solutions by 96 channel distributor
  • (Oscillate)
  • Centrifuge
  • Distribute building blocks and reagents
    • multichannel pipetting or Multiprobe 104
  • Oscillate
  • Centrifuge
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Synthesis Algorithm (continuation)
  • Remove protecting groups
  • Wash plates in centrifuge
  • Dry resin in plates in vacuum
  • Place plates in HF chamber or distribute cleavage solution by 96 channel distributor
  • Dry resin in plates in vacuum
  • Extract product (reformat, take analytical samples)
  • Evaporate or lyophilize product
  • Seal microtiterplates
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HF Chamber for Parallel Cleavage (“Bazooka”)
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Betides - Examples of Results
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Tetrahydroisoquinolinones
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Tetrahydroisoquinolinones
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How About Tomorrow ?

When and where can I get one of these instruments?
  • One COMPAS at each chemist’s bench
    • modular approach
      • simple centrifuge up to fully automatic machine
      • from mg to kg scale
  • Partner for commercialization ...
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Illumina’s Revolutionary Technology:
Bringing Fiber Optics to Biology
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Fiber Bundles:  Flexible Platform
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Scalability of Technology
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Custom Oligo Price History
  • 1972 $1,667.00/base
  • 1989 $     10.00/base
  • 1992 $       3.50/base
  • 1994 $       2.19/base
  • 1996 $       1.50/base
  • 1999 $       0.75/base
  • 2000 $       0.60/base
  • 2001 $       0.24/base (Illumina)
  • 2002 $       0.16/base (Illumina)
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First Generation OligatorTM Prototype
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Carbon Fiber Rotor
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Third Generation of Oligator 768TM
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From 4 L Flasks to 1250 L Drums
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QC of Oligator Production: MS
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QC of Oligator Production: HPLC
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Coupling Efficiencies
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HPLC Traces of Unpurified 25-mer Oligos
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HPLC Trace of Unpurified 25-mer Oligos
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Commercial Interlude
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The Oligator FarmTM Services
  • Custom oligo synthesis for large consumers
  • Current capacity > 400M bases per year
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We Are Shipping Oligos Daily!
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Conclusions
  • Tilted centrifugation is the most effective and simplest method for liquid removal and phase separation in multiplicity of vessels
  • Polypropylene microtiterplates are ideal reaction vessels for tilted centrifugation based synthesis
  • Tilted centrifugation is the only way for removal of liquids in ultraminiaturized techniques
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"Centrifugation:"
  • Centrifugation:
  • The Only Technique
  •  for
  • Massively Parallel Solid Phase Synthesis
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