Flash Chromatography

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Flash Chromatography

• 150 300 ml/min Flash Pumps
• New 200 ml/min Binary Flash Pump

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Flash 300

• SPECIFICATIONS
• Flow Rate . . . . . .. . 0.1 300.0 ml/min
• Max. Pressure . . . . 200 p.s.i.
• Flow Accuracy . . . 3 (10 250 ml/min)
• Dimensions . . . . . . 7.0" W x 12.0" D x 7.5" H
• Weight . . . . . . . . . . 20 lbs

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Flash 300 Performance Data
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Flash 300 Features

• Dual-Head Design for High Flow Low Pulsation
• Ceramic Pistons and High Performance UHMW,
  HPLC-grade Seals
• Ruby Ball / Sapphire Seat Check Valves
• Universal Voltage Input 90 260 VAC / 50
  60 Hz
• Constant Flow Performance with Varying Back
  Pressure
• Accurate Flow Rate and No Loss of Prime with
  Hexane, Methylene Chloride and other Light
  Solvents
• Combination Prime-Purge Valve / T /
  Single-Port Outlet (1/8)
• Additional Outlet Check Valve to Prevent
  Backflow during Priming
• All-Stainless Steel Fluid Path (unless
  otherwise indicated pistons, check valves
  seals)
• Fluid Path Isolated from Electrical Components
• Interactive Digital Keypad, RS-232 PC Control
  Monitoring, Remote Run/Stop
• Fine-Tune Flow Calibration Set-Up Function 2
  increments to 10 at 300 ml/min
• EZChrom Driver available

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Compatible with Gradient Flash

• Use the SCU 470 for stand alone gradient
• 600ml/min isocratic
• 300ml/min gradients
• VUV 14 or Model 500 detector optional

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Simplicity and Function
       
 
Calibration Button
Run / Stop Button
Power Switch
                           
 

Pump Inlet / Outlet Check Valve Holders   One
Capsule per Holder
Pump Inlet / Outlet Check Valve Holders   One
Capsule per Holder
Inlet (flexible tubing provided)
Prime-Purge Valve
Check Valve to Prevent Back Flow During Priming
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Calibrate for Any Solvent
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Flash 150 Binary Pump

• 2 pumps in one cabinet
• 150 ml/min for gradient
• 300 ml/min isocratic
• 150 p.s.i. max
• Low cost for the flow range
• Allows use of larger columns than other Binary
  pumping system

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NEW Binary Flash 200

• SPECIFICATIONS
• Pumps . . . . . .. .. 2
• Flow Rate . . . . . .. . 0.1 200.0 ml/min each
  pump
• Max. Pressure . . . . 200 p.s.i.
• Flow Accuracy . . . 3 (10 200 ml/min)
  Dimensions . . . . . . 7.0" W x 12.0" D x 7.5" H
• Weight . . . . . . . . . . 20 lbs

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Binary Flash 150 200 Features

• Two Single-Head Pumps with Electronic
  Fast-Refill for Low Pulsation in a Compact
  Package
• Ceramic Pistons and High Performance UHMW,
  HPLC-grade Seals
• Ruby Ball / Sapphire Seat Check Valves
• Universal Voltage Input 90 260 VAC / 50
  60 Hz
• Constant Flow Performance with Varying Back
  Pressure
• Accurate Flow Rate and No Loss of Prime with
  Hexane, Methylene Chloride and other Light
  Solvents
• Combination Prime-Purge Valve / T /
  Single-Port Outlet (1/8)
• Additional Outlet Check Valve to Prevent
  Backflow during Priming
• All-Stainless Steel Fluid Path (unless
  otherwise indicated pistons, check valves
  seals)
• Fluid Path Isolated from Electrical Components
• Interactive Digital Keypad, RS-232 PC Control
  Monitoring, Remote Run/Stop
• Fine-Tune Flow Calibration Set-Up Function 2
  increments to 10 at max flow
• EZChrom Driver available

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Flash Chromatography Today Demands

• Higher throughput
• Higher purity requirements
• More Compounds purified in less time
• A wider variety of compound types to separate

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Organic Chemists Face the Following Challenges

• Little time to develop chromatography
• Minimal interaction with instrumentation
• Low solubility of compounds in water
• Aqueous solvents incompatible with the next
  reaction
• Difficult to remove water and alcohol
• Very familiar with TLC
• no time to optimize separation conditions

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Organic Chemists Require

• High quantities of material
• High loads
• Systems for samples soluble in NP solvents
• Must deal with low solubility and high volumes
• Ever increasing purity requirements
• Disposable columns
• Simple to use hardware

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Today's Synthetic Reality

• Modern synthesis is a multi step process
• Purification between steps increases purity and
  yield
• Except in biological synthesis samples are not RP
  compatible
• HPLC is too expensive and sophisticated for
  synthesis purification
• Old style flash is not fast enough nor giving
  high enough purity

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Unique Problems with Flash

• Sample Load
• Sample Solubility
• Incompatibility of sample solvent with
  purification method

Let the Flash 150, 200 300 solve these problems
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Volume Load Effects

• Compared to analytical chemistry
• Chemists require high sample loading (10mg-100s
  gram)
• End goal may only be 10 mg but may require 50-100
  grams of starting material
• Sample solubility problems require the use of
  solvents that are strong (cause elution of
  product)

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Loading Volume and Band-Broadening

• Same sample loaded with constant mass
• 150 mg load
• Three different cartridges
• Chromatogram A
• Loading volume equivalent to 3 of column void
  volume (36 mL)
• Chromatogram B
• Loading volume equivalent to 22 column void
  volume
• Chromatogram C
• Loading volume equivalent to 50 column void
  volume
• High volume Loads destroy the separation

Minutes
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Large Volume Loads Reduce Resolution

• Illustrates the effect of sample volume on
  separation of component B from A
• Sample load volume, as a percentage of void
  volume (Load Vol./Void Vol.), was plotted vs.
  resolution
• Resolution degrades when sample load increase to
  20 of the column void volume
• Keep load at lt20 of column volume

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Flash 150, 200 300 Solution to Loading Problems

• Allows bigger columns so sample can be less than
  20 of column void

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High Mass Loading Destroys Separation

• Sample volume was kept constant
• 2 mL in 80/20 acetonitrile-water
• Effect of sample load increase shown
• As mass increases, peak fronts shift
• Peak tails overlap as mass increases
• Load determines Column Size required

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Impact of Sample Mass on Separation

• Ratio between loading mass and amount of packing
  material, Sample Mass/Packing (), is shown vs.
  retention behavior
• When loading mass increases over 1.5 of the
  packing material, peak asymmetry increase
  significantly
• Retention shifts to front as loading mass
  increases
• As loading mass increases, peak tails overlap
  (without shifting)

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Solvent and Co-Elution Reduces Loading
A
Co-elution
B

• A detailed fraction analysis for an affected
  purification
• Total sample load 120 mg for components A and B
• Sample dissolved in 0.8 mL dichloromethane
• 955 Hexane-Ethyl Acetate as eluting solvent
• Fractions are collected 1.3 mL/fraction
• Fraction purity was analyzed using HPLC and
  plotted vs. fraction number

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Flash 150, 200 300 Advantage

• Allows column size to be matched to load with out
  sacrificing time due to low flows

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Organic Synthesis Trends

• Organic chemists face rapidly changing,
  conflicting needs
• More Synthesis
• Greater output
• Higher synthesis purity
• Greater synthesis yields
• A synthesis catch-22 dilemma

More products/day
Increased product yields
Higher product purity
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Flash 150, 200 300 Changes the Game

• Bridges the flash to prep HPLC gap
• Allows a new approach to flash based on
• Higher pressures
• Gradient
• More efficiency

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Effect of Particle Size on Efficiency

• 13-20 micron particles give optimal prep
  efficiency

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Effect of Efficiency on Resolution

• Must square the number of theoretical plates to
  double resolution
• Loading reduces high plate column efficiency
  faster than lower plate columns

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Capacity K

• Measured in column volume
• Think in terms of column volumes of retention
• Solvent strength effects k
• Gradient changes k with time from infinity to
  less than 1

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Factors Affecting Capacity

• Surface Area
• Porosity
• Particle density
• Size
• Active coating coverage
• Solvent strength

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Effect of Particle Size on Pressure

• Doubling particle size reduces pressure by a
  factor of 4 at the same linear velocity
• Flash 200 300 allow 16-20 micron particles to
  be used
• Higher efficiency in the same time with more
  surface area

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Flash 150, 200 300 Advantage

• The 200psi pressure limit allows smaller
  particles and higher resolution
• Capacity can be dramatically Improved
• Beat the CATCH 22 by using the Flash 200 300
  benefits

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Gradient Effects

• Can further dramatically increase through put by
  allowing full use of the column for purification.
• Can actually shorten separation time.
• Can concentrate samples

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Flash 300 200 150 Advantage

• Can use SCU470 for stand alone gradient control
• High flow in isocratic mode 600ml/min for 2
  Flash 300 and 400ml/min for Flash 200
• Gradient is now reasonable for Flash Separations

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SSI Offers

• Single channel systems
• Increase capability at moderate costs
• A series of pumps for flash chromatography
• System capability

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Flash 150, 200 300 Summary

• Allows bigger columns so sample can be less than
  20 of column void
• Allows column sized to be matched to load with
  out sacrificing time due to low flows
• The 200psi pressure limit allows smaller
  particles and higher resolution
• Allows gradients
• Easy calibration for a wide variety of solvents
• Simplicity of design for reliable performance