Flash ChromatographyFlash Chromatography

150 & 300 ml/min Flash 150 & 300 ml/min Flash PumpsPumps

New 200 ml/min Binary New 200 ml/min Binary Flash PumpFlash Pump

Flash 300Flash 300

SPECIFICATIONSSPECIFICATIONS

• Flow RateFlow Rate . . . . . .. . 0.1 – 300.0 ml/min . . . . . .. . 0.1 – 300.0 ml/min

• Max. PressureMax. Pressure . . . . 200 p.s.i. . . . . 200 p.s.i.

• Flow AccuracyFlow Accuracy . . . . . . ++ 3% (10 – 250 ml/min) 3% (10 – 250 ml/min)

• DimensionsDimensions . . . . . . 7.0" W x 12.0" D x 7.5" . . . . . . 7.0" W x 12.0" D x 7.5" HH

• Weight Weight . . . . . . . . . . 20 lbs. . . . . . . . . . 20 lbs

Flash 300 – Performance Flash 300 – Performance DataData

Flash 300 FeaturesFlash 300 Features• Dual-Head Design for High Flow & Low PulsationDual-Head Design for High Flow & Low Pulsation

• Ceramic Pistons and High Performance UHMW, HPLC-grade SealsCeramic Pistons and High Performance UHMW, HPLC-grade Seals

• Ruby Ball / Sapphire Seat Check Valves Ruby Ball / Sapphire Seat Check Valves

• Universal Voltage InputUniversal Voltage Input: 90 – 260 VAC / 50 – 60 Hz: 90 – 260 VAC / 50 – 60 Hz

• Constant Flow Performance with Varying Back PressureConstant Flow Performance with Varying Back Pressure

• Accurate Flow Rate and No Loss of Prime with Hexane, Methylene Chloride and other Accurate Flow Rate and No Loss of Prime with Hexane, Methylene Chloride and other Light Solvents Light Solvents

• Combination Prime-Purge Valve / ”T” / Single-Port Outlet (1/8”)Combination Prime-Purge Valve / ”T” / Single-Port Outlet (1/8”)

• Additional Outlet Check Valve to Prevent Backflow during PrimingAdditional Outlet Check Valve to Prevent Backflow during Priming

• All-Stainless Steel Fluid Path (unless otherwise indicated – pistons, check valves & All-Stainless Steel Fluid Path (unless otherwise indicated – pistons, check valves & seals) seals)

• Fluid Path Isolated from Electrical ComponentsFluid Path Isolated from Electrical Components

• Interactive Digital Keypad, RS-232 PC Control & Monitoring, Remote Run/StopInteractive Digital Keypad, RS-232 PC Control & Monitoring, Remote Run/Stop

• Fine-Tune Flow Calibration Set-Up Function:Fine-Tune Flow Calibration Set-Up Function: 2% increments to ±10% at 300 2% increments to ±10% at 300 ml/minml/min

• EZChromEZChrom Driver available Driver available

Compatible with Gradient Compatible with Gradient FlashFlash

• Use the SCU 470 for Use the SCU 470 for stand alone gradientstand alone gradient

• 600ml/min isocratic600ml/min isocratic

• 300ml/min gradients300ml/min gradients

• VUV 14 or Model 500 VUV 14 or Model 500 detector optionaldetector optional

Simplicity and FunctionSimplicity and FunctionPower Switch

Run / StopButton

Inlet(flexible tubing provided)

Prime-PurgeValve

Check Valve to Prevent Back Flow

During Priming

Pump Inlet / Outlet Check Valve Holders

 

One Capsule per Holder

Calibration Button

Pump Inlet / Outlet Check Valve Holders

 

One Capsule per Holder

 

    

 

 

             

Calibrate for Any SolventCalibrate for Any SolventFlash Pump FlowRate vs Comp Setting

-10.000

-5.000

0.000

5.000

10.000

15.000

10

30

50

70

90

110

13

0

15

0

17

0

19

0

21

0

23

0

25

0

27

0

29

0

Flowrate (ml/min)

% o

f F

low

rate

ch

an

ge

1 2 3 4 5 6 7 8 9 10

Flash 150 Binary PumpFlash 150 Binary Pump

• 2 pumps in one cabinet2 pumps in one cabinet

• 150 ml/min for gradient150 ml/min for gradient

• 300 ml/min isocratic300 ml/min isocratic

• 150 p.s.i. max150 p.s.i. max

• Low cost for the flow Low cost for the flow rangerange

• Allows use of larger Allows use of larger columns than other columns than other Binary pumping systemBinary pumping system

NEWNEW Binary Flash 200 Binary Flash 200

SPECIFICATIONSSPECIFICATIONS

• # Pumps # Pumps . . . . . .. .. 2. . . . . .. .. 2

• Flow RateFlow Rate . . . . . .. . 0.1 – 200.0 ml/min each . . . . . .. . 0.1 – 200.0 ml/min each pumppump

• Max. PressureMax. Pressure . . . . 200 p.s.i. . . . . 200 p.s.i.

• Flow AccuracyFlow Accuracy . . . . . . ++ 3% (10 – 200 ml/min) 3% (10 – 200 ml/min) DimensionsDimensions . . . . . . 7.0" W x 12.0" D x 7.5" H . . . . . . 7.0" W x 12.0" D x 7.5" H

• Weight Weight . . . . . . . . . . 20 lbs . . . . . . . . . . 20 lbs

Binary Flash 150 & 200 Binary Flash 150 & 200 FeaturesFeatures• Two Single-Head Pumps with Electronic Fast-Refill for Low Pulsation in a Compact Two Single-Head Pumps with Electronic Fast-Refill for Low Pulsation in a Compact

PackagePackage

• Ceramic Pistons and High Performance UHMW, HPLC-grade SealsCeramic Pistons and High Performance UHMW, HPLC-grade Seals

• Ruby Ball / Sapphire Seat Check Valves Ruby Ball / Sapphire Seat Check Valves

• Universal Voltage InputUniversal Voltage Input: 90 – 260 VAC / 50 – 60 Hz: 90 – 260 VAC / 50 – 60 Hz

• Constant Flow Performance with Varying Back PressureConstant Flow Performance with Varying Back Pressure

• Accurate Flow Rate and No Loss of Prime with Hexane, Methylene Chloride and Accurate Flow Rate and No Loss of Prime with Hexane, Methylene Chloride and other other Light Solvents Light Solvents

• Combination Prime-Purge Valve / ”T” / Single-Port Outlet (1/8”)Combination Prime-Purge Valve / ”T” / Single-Port Outlet (1/8”)

• Additional Outlet Check Valve to Prevent Backflow during PrimingAdditional Outlet Check Valve to Prevent Backflow during Priming

• All-Stainless Steel Fluid Path (unless otherwise indicated – pistons, check valves & All-Stainless Steel Fluid Path (unless otherwise indicated – pistons, check valves & seals) seals)

• Fluid Path Isolated from Electrical ComponentsFluid Path Isolated from Electrical Components

• Interactive Digital Keypad, RS-232 PC Control & Monitoring, Remote Run/StopInteractive Digital Keypad, RS-232 PC Control & Monitoring, Remote Run/Stop

• Fine-Tune Flow Calibration Set-Up Function:Fine-Tune Flow Calibration Set-Up Function: 2% increments to ±10% at max 2% increments to ±10% at max flowflow

• EZChromEZChrom Driver available Driver available

Flash Chromatography Today Flash Chromatography Today DemandsDemands

• Higher throughputHigher throughput• Higher purity requirementsHigher purity requirements• More Compounds purified in More Compounds purified in

less timeless time• A wider variety of compound A wider variety of compound

types to separatetypes to separate

Organic Chemists Face the Following Organic Chemists Face the Following ChallengesChallenges• Little time to develop chromatographyLittle time to develop chromatography• Minimal interaction with instrumentationMinimal interaction with instrumentation• Low solubility of compounds in waterLow solubility of compounds in water• Aqueous solvents incompatible with the Aqueous solvents incompatible with the

next reactionnext reaction• Difficult to remove water and alcoholDifficult to remove water and alcohol• Very familiar with TLCVery familiar with TLC• no time to optimize separation no time to optimize separation

conditionsconditions

Organic Chemists RequireOrganic Chemists Require

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

Today's Synthetic RealityToday's Synthetic Reality

• Modern synthesis is a multi step processModern synthesis is a multi step process

• Purification between steps increases purity and Purification between steps increases purity and yieldyield

• Except in biological synthesis samples are not RP Except in biological synthesis samples are not RP compatiblecompatible

• HPLC is too expensive and sophisticated for HPLC is too expensive and sophisticated for synthesis purificationsynthesis purification

• Old style flash is not fast enough nor giving high Old style flash is not fast enough nor giving high enough purityenough purity

Unique Problems with Unique Problems with FlashFlash

• Sample LoadSample Load• Sample SolubilitySample Solubility• Incompatibility of sample solvent with Incompatibility of sample solvent with

purification methodpurification method

Let the Flash 150, 200 & 300 solve these problems

Volume Load EffectsVolume Load Effects

• Compared to analytical chemistry Compared to analytical chemistry – Chemists require high sample loading (10mg-100’s Chemists require high sample loading (10mg-100’s

gram)gram)• End goal may only be 10 mg but may require 50-100 End goal may only be 10 mg but may require 50-100

grams of starting materialgrams of starting material

– Sample solubility problems require the use of solvents Sample solubility problems require the use of solvents that are strong (cause elution of product)that are strong (cause elution of product)

Loading Volume and Band-Loading Volume and Band-BroadeningBroadening

Minutes

150 mg in 18 mL AU

0

1.00

1.80

1.0 2.0 3.0 4.0 5.0 6.0 7.0 8.0 9.0 10

C

150 mg in 8 mL

AU

0

1.00

1.80

1.0 2.0 3.0 4.0 5.0 6.0 7.0 8.0 9.0 10

B

150 mg in 1 mL

AU

0

1.00

1.80

1.0 2.0 3.0 4.0 5.0 6.0 7.0 8.0 9.0 10

A Desired product • Same sample loaded with Same sample loaded with constant mass:constant mass:– 150 mg load150 mg load– Three different cartridgesThree different cartridges

• Chromatogram A: Chromatogram A: – Loading volume equivalent to Loading volume equivalent to

3% of column void volume (36 3% of column void volume (36 mL)mL)

• Chromatogram B:Chromatogram B:– Loading volume equivalent to Loading volume equivalent to

22% column void volume22% column void volume• Chromatogram C:Chromatogram C:

– Loading volume equivalent to Loading volume equivalent to 50% column void volume50% column void volume

High volume Loads destroy the High volume Loads destroy the separationseparation

Large Volume Loads Reduce Large Volume Loads Reduce ResolutionResolution

0102030405060708090

100

0 5 10 15 20 25 30 35 40 45 50 55

Load Vol./Void Vol. (% )

Re

so

luti

on

(%

)

p

2.88

6

3.75

3

6.12

3

A

B

C

• Illustrates the effect of sample Illustrates the effect of sample volume on separation of volume on separation of component B from Acomponent B from A

• Sample load volume, as a Sample load volume, as a percentage of void volume percentage of void volume (Load Vol./Void Vol.), was (Load Vol./Void Vol.), was plotted vs. resolutionplotted vs. resolution

• Resolution degrades when Resolution degrades when sample load increase to 20% sample load increase to 20% of the column void volumeof the column void volume

Keep load at <20% of Keep load at <20% of column volumecolumn volume

Flash 150, 200 & 300 Solution Flash 150, 200 & 300 Solution to Loading Problemsto Loading Problems• Allows bigger columns so sample can be Allows bigger columns so sample can be

less than 20% of column void less than 20% of column void

High Mass Loading Destroys High Mass Loading Destroys SeparationSeparation

mV

0

20

40

60

80

100

120

Minutes1.0 1.5 2.0 2.5 3.0 3.5 4.0 4.5 5.0 5.5 6.0 6.5 7.0

Mass loaded (mg)

1600140012001000

800700600400300200100

50

Desired component • Sample volume was Sample volume was kept constantkept constant– 2 mL in 80/20 2 mL in 80/20

acetonitrile-wateracetonitrile-water• Effect of sample load Effect of sample load

increase shown:increase shown:– As mass increases, As mass increases,

peak fronts shiftpeak fronts shift– Peak tails overlap as Peak tails overlap as

mass increasesmass increases

Load determines Load determines Column Size requiredColumn Size required

Impact of Sample Mass on Impact of Sample Mass on SeparationSeparation

2.0

2.5

3.0

3.5

4.0

4.5

5.0

5.5

6.0

6.5

0.0 0.5 1.0 1.5 2.0 2.5 3.0 3.5

Sample Mass/Packing (%)

Re

ten

tio

n (

min

.)

Retention at Peak Max

Retention at Peak Tail

Asymmetry (10%)

• 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)

Solvent and Co-Elution Reduces Solvent and Co-Elution Reduces LoadingLoading

1.4

25

3.5

96120 mg (A+B) in 0.8 mL DCM On 12+M

0%

10%

20%

30%

40%

0 5 10 15 20 25 30

Fraction number

Ma

ss Area A3 (%)

Area B3 (%)

[A3+B3] (%)

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• 95:5 Hexane-Ethyl Acetate as eluting solvent• Fractions are collected: 1.3 mL/fraction• Fraction purity was analyzed using HPLC and plotted vs. fraction number

AB

Co-elution

Flash 150, 200 & 300 Flash 150, 200 & 300 AdvantageAdvantage• Allows column size to be matched to Allows column size to be matched to

load with out sacrificing time due to low load with out sacrificing time due to low flowsflows

Organic Synthesis Trends Organic Synthesis Trends

• Organic chemists’ Organic chemists’ face rapidly face rapidly changing, conflicting changing, conflicting needsneeds– More SynthesisMore Synthesis– Greater output Greater output – Higher synthesis Higher synthesis

puritypurity– Greater synthesis Greater synthesis

yieldsyields

• A synthesis catch-22 A synthesis catch-22 dilemmadilemma

Increased product yields

Higher product purity

More products/day

Synthesis catch-22

Flash 150, 200 & 300 Changes the Flash 150, 200 & 300 Changes the GameGame

• Bridges the flash to prep HPLC gapBridges the flash to prep HPLC gap

• Allows a new approach to flash based Allows a new approach to flash based on:on:– Higher pressuresHigher pressures– GradientGradient– More efficiencyMore efficiency

Effect of Particle Size on Effect of Particle Size on EfficiencyEfficiency• 13-20 micron particles give optimal prep 13-20 micron particles give optimal prep

efficiencyefficiency

Effect of Efficiency on Effect of Efficiency on ResolutionResolution• Must square the Must square the

number of number of theoretical plates to theoretical plates to double resolutiondouble resolution

• Loading reduces high Loading reduces high plate column plate column efficiency faster than efficiency faster than lower plate columnslower plate columns

Capacity K’Capacity K’

• Measured in column Measured in column volumevolume

• Think in terms of column Think in terms of column volume’s of retentionvolume’s of retention

• Solvent strength effects Solvent strength effects k’k’

• Gradient changes k’ with Gradient changes k’ with time from infinity to less time from infinity to less than 1than 1

Factors Affecting CapacityFactors Affecting Capacity

• Surface AreaSurface Area

• PorosityPorosity

• Particle densityParticle density

• SizeSize

• Active coating coverageActive coating coverage

• Solvent strengthSolvent strength

Effect of Particle Size on Effect of Particle Size on PressurePressure• Doubling particle size Doubling particle size

reduces pressure by a reduces pressure by a factor of 4 at the same factor of 4 at the same linear velocitylinear velocity

• Flash 200 & 300 allow Flash 200 & 300 allow 16-20 micron particles 16-20 micron particles to be usedto be used

• =Higher efficiency in =Higher efficiency in the same time with the same time with more surface areamore surface area

Particle size Pressure5 2000

10 50020 12540 3180 8

Pressure Vs Particle Size

0

500

1000

1500

2000

2500

0 20 40 60 80 100

Particle size

Pressure

Flash 150, 200 & 300 Flash 150, 200 & 300 AdvantageAdvantage• The 200psi pressure limit allows smaller The 200psi pressure limit allows smaller

particles and higher resolutionparticles and higher resolution

• Capacity can be dramatically ImprovedCapacity can be dramatically Improved

• Beat the CATCH 22 by using the Flash Beat the CATCH 22 by using the Flash 200 & 300 benefits200 & 300 benefits

Gradient EffectsGradient Effects

• Can further dramatically increase Can further dramatically increase through put by allowing full use of the through put by allowing full use of the column for purification.column for purification.

• Can actually shorten separation time.Can actually shorten separation time.

• Can concentrate samplesCan concentrate samples

Flash 300 & 200 & 150 Flash 300 & 200 & 150 AdvantageAdvantage• Can use SCU470 for stand alone Can use SCU470 for stand alone

gradient controlgradient control

• High flow in isocratic mode = High flow in isocratic mode = 600ml/min for 2 Flash 300 and 600ml/min for 2 Flash 300 and 400ml/min for Flash 200400ml/min for Flash 200

• Gradient is now reasonable for Flash Gradient is now reasonable for Flash SeparationsSeparations

SSI Offers SSI Offers

• Single channel systems Single channel systems

• Increase capability at moderate costsIncrease capability at moderate costs

• A series of pumps for flash A series of pumps for flash chromatographychromatography

• System capabilitySystem capability

Flash 150, 200 & 300 Flash 150, 200 & 300 SummarySummary• Allows bigger columns so sample can be less Allows bigger columns so sample can be less

than 20% of column void than 20% of column void • Allows column sized to be matched to load with Allows column sized to be matched to load with

out sacrificing time due to low flowsout sacrificing time due to low flows• The 200psi pressure limit allows smaller The 200psi pressure limit allows smaller

particles and higher resolutionparticles and higher resolution• Allows gradientsAllows gradients• Easy calibration for a wide variety of solventsEasy calibration for a wide variety of solvents• Simplicity of design for reliable performanceSimplicity of design for reliable performance