Flash Chromatography

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

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

Flash 300 Performance Data

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

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

Simplicity and Function

Power Switch Calibration Button Run / Stop Button

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

Calibrate for Any Solvent

Flash Pump FlowRate vs Comp Setting
15.000

% of Flowrate change

10.000 5.000 0.000 -5.000 -10.000

110

130

150

170

190

210

230

250

270

Flowrate (ml/min)
1 2 3 4 5 6 7 8 9 10

290

10

30

50

70

90

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

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

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

Flash Chromatography Today Demands

Higher throughput Higher purity requirements More Compounds purified in less

time A wider variety of compound types to separate

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

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

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

Unique Problems with Flash

Sample Load Sample Solubility Incompatibility of sample solvent with
purification method

Let the Flash 150, 200 & 300 solve these problems

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)

Loading Volume and Band-Broadening

1.80

A
AU 1.00

Desired product 150 mg in 1 mL

Same sample loaded with constant mass: Chromatogram A:

150 mg load Three different cartridges

0 1.0 1.80 2.0 3.0 4.0 5.0 6.0 7.0 8.0 9.0 10

Chromatogram B:

Loading volume equivalent to 3% of column void volume (36 mL) Loading volume equivalent to 22% column void volume Loading volume equivalent to 50% column void volume

B
AU 1.00

150 mg in 8 mL

Chromatogram C:

High volume Loads destroy the

0 1.80 1.0 2.0 3.0 4.0 5.0 6.0 7.0 8.0 9.0 10

separation

C
AU 1.00

150 mg in 18 mL

0 1.0 2.0 3.0 4.0 5.0 6.0 7.0 8.0 9.0 10

Minutes

Large Volume Loads Reduce Resolution

2.886

Illustrates the effect of sample

3.753

6.123

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

100 90 80 70 60 50 40 30 20 10 0 0 5 10 15 20 25 30 35 40 45 50 55 Load Vol./Void Vol. (% )

Resolution degrades when

sample load increase to 20% of the column void volume column volume

Resolution (%)

Keep load at <20% of

Flash 150, 200 & 300 Solution to Loading Problems

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

High Mass Loading Destroys Separation

120 100 80 mV 60 40 20 0 1.0 1.5 2.0 2.5 3.0 3.5 4.0 Minutes 4.5 5.0 5.5 6.0

Desired component

Mass loaded (mg)

1600 1400 1200 1000 800 700 600 400 300 200 100 50
6.5 7.0

Sample volume was kept

constant

Effect of sample load increase shown:

2 mL in 80/20 acetonitrile-water As mass increases, peak fronts shift Peak tails overlap as mass increases

Load determines Column

Size required

Impact of Sample Mass on Separation

6.5 6.0 5.5
Retention (min.)

5.0 4.5 4.0 3.5 3.0 2.5 2.0 0.0 0.5 1.0 1.5 2.0 2.5 3.0 3.5

Retention at Peak Max Retention at Peak Tail Asymmetry (10%)

Sample Mass/Packing (%)

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 Loading

120 mg (A+B) in 0.8 mL DCM On 12+M
40%

1.425

Co-elution

30%

B
Area A3 (%) Area B3 (%) [A3+B3] (%)

Mass

20%

10%

0% 0 5 10 15 20 25 30

Fraction number

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

3.596

Flash 150, 200 & 300 Advantage

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

Organic Synthesis Trends

Organic chemists face
rapidly changing, conflicting needs More Synthesis Greater output Higher synthesis purity Greater synthesis yields
More products/day

Synthesis catch-22

Higher product purity

Increased product yields

A synthesis catch-22
dilemma

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

Effect of Particle Size on Efficiency

13-20 micron particles give optimal prep efficiency

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

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

Factors Affecting Capacity

Surface Area Porosity Particle density Size Active coating coverage Solvent strength

Effect of Particle Size on Pressure

Doubling particle size
Particle size 5 10 20 40 80
2500 2000 1500 1000 500 0 0 20 40 60 80 100 Particle size Pressure

reduces pressure by a factor of 4 at the same linear velocity Flash 200 & 300 allow 1620 micron particles to be used =Higher efficiency in the same time with more surface area

Pressure 2000 500 125 31 8

Pressure Vs Particle Size

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

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

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

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

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