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

Flash 300 SPECIFICATIONS Flow Rate – ml/min Flow Rate – ml/min Max. Pressure p.s.i. Max. Pressure p.s.i. Flow Accuracy % (10 – 250 ml/min) Flow Accuracy % (10 – 250 ml/min) Dimensions " W x 12.0" D x 7.5" H Dimensions " W x 12.0" D x 7.5" H Weight lbs Weight lbs

Flash 300 – Performance Data

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

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

Simplicity and Function Power Switch Run / Stop Button Inlet (flexible tubing provided) Prime-Purge Valve 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 Solvent

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

NEW Binary Flash 200 SPECIFICATIONS # Pumps # Pumps Flow Rate – ml/min each pump Flow Rate – ml/min each pump Max. Pressure p.s.i. Max. Pressure p.s.i. Flow Accuracy % (10 – 200 ml/min) Dimensions " W x 12.0" D x 7.5" H Flow Accuracy % (10 – 200 ml/min) Dimensions " W x 12.0" D x 7.5" H Weight lbs Weight lbs

Binary Flash 150 & 200 Features Two Single-Head Pumps with Electronic Fast-Refill for Low Pulsation in a Compact Package Two Single-Head Pumps with Electronic Fast-Refill for Low Pulsation in a Compact Package Ceramic Pistons and High Performance UHMW, HPLC-grade Seals Ceramic Pistons and High Performance UHMW, HPLC-grade Seals Ruby Ball / Sapphire Seat Check Valves Ruby Ball / Sapphire Seat Check Valves Universal Voltage Input: 90 – 260 VAC / 50 – 60 Hz Universal Voltage Input: 90 – 260 VAC / 50 – 60 Hz Constant Flow Performance with Varying Back Pressure Constant Flow Performance with Varying Back Pressure Accurate Flow Rate and No Loss of Prime with Hexane, Methylene Chloride and other Light Solvents 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”) Combination Prime-Purge Valve / ”T” / Single-Port Outlet (1/8”) Additional Outlet Check Valve to Prevent Backflow during Priming Additional Outlet Check Valve to Prevent Backflow during Priming All-Stainless Steel Fluid Path (unless otherwise indicated – pistons, check valves & seals) All-Stainless Steel Fluid Path (unless otherwise indicated – pistons, check valves & seals) Fluid Path Isolated from Electrical Components Fluid Path Isolated from Electrical Components Interactive Digital Keypad, RS-232 PC Control & Monitoring, Remote Run/Stop 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 Fine-Tune Flow Calibration Set-Up Function: 2% increments to ±10% at max flow EZChrom Driver available EZChrom Driver available

Flash Chromatography Today Demands Higher throughput Higher throughput Higher purity requirements Higher purity requirements More Compounds purified in less time More Compounds purified in less time A wider variety of compound types to separate A wider variety of compound types to separate

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

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

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

Unique Problems with Flash Sample Load Sample Load Sample Solubility Sample Solubility Incompatibility of sample solvent with purification method Incompatibility of sample solvent with purification method Let the Flash 150, 200 & 300 solve these problems

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

Loading Volume and Band-Broadening Minutes 150 mg in 18 mL AU C 150 mg in 8 mL AU B 150 mg in 1 mL AU A Desired product Same sample loaded with constant mass: Same sample loaded with constant mass: –150 mg load –Three different cartridges Chromatogram A: Chromatogram A: –Loading volume equivalent to 3% of column void volume (36 mL) Chromatogram B: Chromatogram B: –Loading volume equivalent to 22% column void volume Chromatogram C: Chromatogram C: –Loading volume equivalent to 50% column void volume  High volume Loads destroy the separation

Large Volume Loads Reduce Resolution pp A B C  Illustrates the effect of sample volume on separation of component B from A 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 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 Resolution degrades when sample load increase to 20% of the column void volume  Keep load at <20% of column volume

Flash 150, 200 & 300 Solution to Loading Problems Allows bigger columns so sample can be less than 20% of column void Allows bigger columns so sample can be less than 20% of column void

High Mass Loading Destroys Separation mV Minutes Mass loaded (mg) Desired component Sample volume was kept constant Sample volume was kept constant –2 mL in 80/20 acetonitrile-water Effect of sample load increase shown: Effect of sample load increase shown: –As mass increases, peak fronts shift –Peak tails overlap as mass increases  Load determines Column Size required

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)

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

Flash 150, 200 & 300 Advantage Allows column size to be matched to load with out sacrificing time due to low flows 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 Organic chemists’ face rapidly changing, conflicting needs –More Synthesis –Greater output –Higher synthesis purity –Greater synthesis yields A synthesis catch-22 dilemma A synthesis catch-22 dilemma Increased product yields Higher product purity More products/day Synthesis catch-22

Flash 150, 200 & 300 Changes the Game Bridges the flash to prep HPLC gap Bridges the flash to prep HPLC gap Allows a new approach to flash based on: Allows a new approach to flash based on: –Higher pressures –Gradient –More efficiency

Effect of Particle Size on Efficiency micron particles give optimal prep efficiency micron particles give optimal prep efficiency

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

Capacity K’ Measured in column volume Measured in column volume Think in terms of column volume’s of retention Think in terms of column volume’s of retention Solvent strength effects k’ Solvent strength effects k’ Gradient changes k’ with time from infinity to less than 1 Gradient changes k’ with time from infinity to less than 1

Factors Affecting Capacity Surface Area Surface Area Porosity Porosity Particle density Particle density Size Size Active coating coverage Active coating coverage Solvent strength Solvent strength

Effect of Particle Size on Pressure Doubling particle size reduces pressure by a factor of 4 at the same linear velocity Doubling particle size reduces pressure by a factor of 4 at the same linear velocity Flash 200 & 300 allow micron particles to be used Flash 200 & 300 allow micron particles to be used =Higher efficiency in the same time with more surface area =Higher efficiency in the same time with more surface area

Flash 150, 200 & 300 Advantage The 200psi pressure limit allows smaller particles and higher resolution The 200psi pressure limit allows smaller particles and higher resolution Capacity can be dramatically Improved Capacity can be dramatically Improved Beat the CATCH 22 by using the Flash 200 & 300 benefits 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 further dramatically increase through put by allowing full use of the column for purification. Can actually shorten separation time. Can actually shorten separation time. Can concentrate samples Can concentrate samples

Flash 300 & 200 & 150 Advantage Can use SCU470 for stand alone gradient control 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 High flow in isocratic mode = 600ml/min for 2 Flash 300 and 400ml/min for Flash 200 Gradient is now reasonable for Flash Separations Gradient is now reasonable for Flash Separations

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

Flash 150, 200 & 300 Summary Allows bigger columns so sample can be less than 20% of column void 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 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 The 200psi pressure limit allows smaller particles and higher resolution Allows gradients Allows gradients Easy calibration for a wide variety of solvents Easy calibration for a wide variety of solvents Simplicity of design for reliable performance Simplicity of design for reliable performance