overview of combiflash product line teledyne isco confidential 1

Teledyne Isco Confidential

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Overview of CombiFlash Product Line


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Agenda

■ Overview

■ Product Availability Dates

■ Pricing

■ Phase out of Current Products

■ Detailed Description of CombiFlash Rf+ PurIon


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Overview

■ CombiFlash Rf 150

■ CombiFlash Rf+

■ CombiFlash Rf+ Lumen

■ CombiFlash Rf+ PurIon

■ CombiFlash Rf Torrent

■ RediSep Rf and RediSep Rf Gold media

■ Foxy R1, R2, and Retriever 500 Fraction Collectors

■ 340 CF ELSD


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Product Availability Dates

■ CombiFlash Rf+

■ CombiFlash Rf+ Lumen

■ CombiFlash Rf+ PurIon

■ Available for customer shipment by October 31st

■ CE Mark by October 31st


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Pricing68-5230-021 CombiFlash Rf+ UV $30,327

68-5230-022 CombiFlash Rf+ UV/Vis $31,269

68-5230-031 CombiFlash Rf+ UV MS Ready $31,587

68-5230-032 CombiFlash Rf+ UV/Vis MS Ready $32,529

68-5230-023 CombiFlash Rf Lumen UV $45,930

68-5230-024 CombiFlash Rf Lumen UV/Vis $47,236

68-5230-033 CombiFlash Rf Lumen UV MS Ready $47,190

685230-034 CombiFlash Rf Lumen UV/Vis MS Ready $48,496

68-5230-041 CombiFlash Rf PurIon UV $98,286

68-5230-042 CombiFlash Rf PurIon UV/Vis $99,167

68-5230-043 CombiFlash Rf PurIon UV with ELSD $118,462

68-5230-044 CombiFlash Rf PurIon UV/Vis with ELSD $119,348


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Phase Out of Current Products

■ Rf 200 and Rf 200i modules will be shipped until the end of December

■ 68-5230-006, 68-5230-008, 68-5230-010, and 68-5230-011

■ Can be quoted until the end of October with a validity of 30 days

■ No orders will be accepted after the end of November

■ No shipments will occur after December 31, 2013


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Introducing the CombiFlash Rf+ PurIon

A Fully Integrated

Flash Chromatography – Mass Spectrometer System


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Topics

■ The Question

■ Partner

■ How Does it Work

■ Functions

■ Control

■ Competition

■ Accessories


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The Question

■ Why use an MS connected in real time to a Flash system? Molecular weight and limited structural information.

The ‘ultimate’ in selectivity.

Visibility of co-eluting contaminants

Mass confirmation of collected fractions to avoid offline TLCs, workup and core lab LC-MS assays.

Characterization of isomeric mixtures.


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Mass Spec vs. other Flash detectors ■ UV – provides a linear response to the concentration of an analyte as long as it absorbs at the available detector UV

wavelengths.■ Response varies by compound/wavelength■ Not all compounds can be detected■ Not selective

■ ELSD measures light scattered from semi- and non-volatile particles that have been dried of mobile phase through

evaporation.■ More universal than UV■ More consistent response than UV since does not have absorption coefficient■ Non-linear response■ Still not selective

■ Mass Spectrometry■ Applicable to a broad range of organic compounds■ As well as providing chromatographic data it identifies the compound by confirming its mass (no advantage if only using TIC!)■ Mass spectrometry has a broad range of utility but is not a universal detector


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Partner

■ Advion selected over 2 years ago as the MS vendor to work with

■ Other companies considered included Microsaic

■ Advion development was most advanced and product was closer to market than others

■ Advion willing to drive toward our cost point target


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Advion

A Leader of Mass Spec and Microfluidic Systems based upon decades of LC/MS expertise

Global HeadquartersIthaca, New York


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The pioneer and leader in nano/micro fluidic ionization sources, flow radiochemistry, and compact mass spectrometry systems.

Expression™ CMS

A compact mass spectrometer for organic chemists, giving them direct access to mass measurement at all steps of solution phase synthetic routes

TriVersa NanoMate®

An automated chip-based nanoelectrospray ion source for high performance/high resolution mass spectrometers. The most versatile sample introduction technique for mass spectrometry.

Chip-Mate

An affordable chip-based nanoelectrospray LC/MS ion source with unique spray-sensing capabilities for maximum robustness

NanoTek®

A microfluidic flow synthesis system for clinical radiochemistry

Until 2012, Advion was North America’s largest LC/MS/MS CRO (sold to Quintiles)


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New product ideas driven by customer requirements, CRO intelligence and synthetic chemistry industry experience

Advion’s CRO included 58 LC/MS/MS serving small molecule analytical Discovery to Phase 4

Advion Scientific Founder’s Cornell research group was the inventor of Ion Spray

Group headed by Dr. Jack Henion

Advion is an expert in Ion Sources and applying them to their best advantage for a variety of applications

Advion CEO, David Patteson, former CEO of Biotage AB


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Developed by small molecule, peptide and natural product MS experts & chemists for chemists A fresh new perspective and an alternative to traditional

MS products Designed for In-Hood use Fast answers in space-restricted labs Does not compromise performance requirements or budgets High Performance, Compact, Affordable Mass Spec Detector

for the chemist

What is different about Advion’s expression Compact MS?


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■ Ion Source: ESI with APCI option (switchable with minimal effort)

■ API: Patented orthogonal ion sampling from heated capillary – allows very high performance with a single small turbo pump

■ Flow rate range: 10 µL/min to 500 µL/min (1 ml/min with APCI using high organic)

■ Polarity: +ve or –ve ion in sequential analyses

■ m/z Range: m/z 10 to m/z 1,200

■ Acquisition rate: 5,000 m/z units sec1 (compatible with UPLC)

■ Resolution: 0.5-0.7 m/z units (FWHM) at 1000 m/z units sec1 over entire acquisition range

■ SIM sensitivity: 10 pg Reserpine (FIA - 5µL sample injection volume at 100 µL/min) 100:1 S/N (RMS) with SIM of m/z 609.28

■ Accuracy: 0.1 m/z units over entire acquisition range

Specifications for CMS – not PurIon


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Components making up a CombiFlash Rf+ PurIon

■ CombiFlash Rf+

■ CombiFlash PurIon Detector Module

■ Fluid Interface

■ Roughing Pump

Pump head

Prime valve Back pressure 40 psi

Pulse damper

To Mass Spec

To Rf port DFrom Rf port C

Pressure Transducer

SplitterValve

Fluid Interface Flow Diagram


FromFluid

Interface

MethodDevelopmentInject Valve

2 µmFilter

IonSource

Method Development to Ion Source



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Under the Cover View

Pulse Damper

Carrier Pump

MRA (Splitter Valve)

PressureTransducer

Back Pressure Regulator

Prime Valve


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Front and Back Panels of Fluid Interface

Power Cables for MS and Rf

USB to Rf

USB from front of MSUSB to back of MS

AC Power Cord

Prime Valve

Carrier Pump

MRA


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Functions/Options

■ Target Mass or Mass Range Detection

■ ESI or APCI

■ Positive or Negative Ionization

■ Pre-purification verification

■ Reaction Monitoring


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Control

■ Single point control via PeakTrak

■ User does not have access to all operating parameters

■ Goal was to keep operation SIMPLE


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MS Settings


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Method Development Screen

■ Pre-purification Verification

■ Reaction Monitoring

■ Flow Injection Analysis


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Flow Injection or Reaction Monitoring

CombiFlash Rf+

Isocratic make up Pump

Column

10 - 200 mL/min Gradient

200 µL/min Methanol with 0.1% Formic Acid

Return to UV

200 µL/minto ESI/APCI Mass Spectrometer

Rheodyne Mass Rate Attenuator (MRA)


FromFluid

Interface

To IonSource

InjectionPort

DrainTube

Inject SamplePosition

5 µl volumetubing

Scan MassPosition

Manual Injection Valve


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MS Tab Options


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Manual Control


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Real Time Run Display


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Past Peak MS Display in Real Time


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Post Run MS


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CombiFlash Rf+ PurIon SpecificationsDimensions (W x H x D) CombiFlash PurIon Mass Detector: cm

Fluid Interface cmCombiFlash Rf+ PurIon system: cmRoughing Pump:

Weight CombiFlash PurIon Mass Detector: kgFluid Interface: kgCombiFlash Rf+: kgRoughing Pump:CombiFlash Rf+ PurIon system: kg

Mass Analyzer Single quadrupoleIonization Source Electrospray ionization (Optional Atmospheric Chemical Ionization)Detection Range m/z 50 – 1200Mass Accuracy ± m/z 0.5 in full scan in a temperature controlled environment, ±3 °CMass Resolution m/z ± 1 Sampling Adjustment AutomaticStart-up Time30 minutes after roughing pump reaching full vacuumVacuum Pumps Integrated Turbo pump, external roughing pumpControl Interface PeakTrakCompatible Systems CombiFlash Rf+ and CombiFlash Rf+ Lumen (Mass Ready) Systems

Upgraded CombiFlash Rf200 Systems Gas Requirement 4.5 - 9 bar N2

Gas Consumption 4 L/minPower Requirement 100–240 V AC; 50–60 Hz


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TypicalMessages


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Typical Messages


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Going from Standby to Operate


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Going from Operate to Standby


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Competition

■ Biotage Isolera Dalton - Introduced September 2012 – Active demos and reported sales

■ Interchim - Introduced January 2012 – Demo at University of Boston in March

■ Agela - Introduced November 2012 – No known activity


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Biotage Isolera DaltonFlash Chromatography with Integrated Mass IdentificationBe sure you have your target compound the moment your purification is complete. Isolera™ Dalton integrates the Biotage approach to flash chromatography with true compound identification using mass detection.For the first time, Flash chemists can automatically collect targeted mass fractions of their compounds on a flash system. Isolera™ Dalton is nothing less than a fully-fledged mass identifier system specifically designed to plug seamlessly into the Isolera™ family.Provided by a company with over twenty years’ experience in Flash chromatography, Isolera Dalton represents the most advanced and innovative purification system available, designed by people who understand Flash purification and the needs of the synthetic chemist.


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Biotage Claims 1

Biotage■ Streamlined Workflow

Isolera Dalton brings mass detection to flash chromatography. This system identifies compounds by mass in real time during Flash separation, leading to greater confidence in purification and a significant saving in time and money. This combination of identification and purification removes complex off-line analytical steps from the workflow, vastly increasing throughput and putting the entire purification and analysis in the hands of the chemist.

■ Reactor content can be injected directly to identify target masses, which then are transferred directly to the Flash method for mass targeted purification.

TIsco


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Biotage Claims 2

BiotageTailored TechnologyIsolera Dalton automates and takes the hard work out of the compound identification and purification, perfect for chemists whose priorities lie more towards the chemistry than small details of running the analysis. Minimal user intervention required makes it available to chemists unfamiliar with mass detection or those whose priorities lie in compound synthesis rather than analysis.

Isolera™ Dalton Mass Detector uses a chip-based electrospray system with a miniaturized quadrupole and internal vacuum pumps, allowing the system to easily fit in a fume hood, and is capable of handling both normal and reverse-phase samples with ease.

TIsco

PurIon system is not miniaturized and requires an external roughing pump – reduces the possibility of plugging


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Biotage Claims 3

BiotageIntelligent IntegrationSeamless interaction between a flash system and a mass detector requires advanced technology and fine tuning. This is all taken care of by the Isolera™ Dalton Nanolink interface, an intelligent sampling device that at any given moment provides Isolera Dalton Mass Detector with the exact amount of sample required, and dynamically adjusts to the solvent effluent flow rate employed in the Flash system.Isolera™ Spektra software with its graphic user interface provides a straightforward controlling environment, giving easy access to the process

TIsco

The Fluid Interface provides control of carrier solvent and switching valve


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Biotage Claims 4

Biotage■ Compound identification by mass during purification

and by direct injection

■ Fully automated integration of Flash purification and mass detection via the Isolera™ Dalton Nanolink

■ Automatically accommodates different flash flow rates

■ Simple wizard-based approach to method development

■ Compact system with miniaturized mass detector, easily fits inside a fume hood with no external pumps

TIsco

Requires an external roughing pump – Biotage does not since they do no offer the option of APCI probe


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Biotage Dalton SpecificationsDimensions (W x H x D) Isolera™ Dalton Mass Detector: 35.5 x 56 x 25 cm

Isolera™ Dalton Nanolink: 35.4 x 52.5 x 21 cmIsolera™ Dalton system: 85 x 59 x 62 cm

Weight Isolera™ Dalton Mass Detector: 32 kgIsolera™ Dalton Nanolink: 10 kgIsolera™: 35 kgIsolera™ Dalton system: 77 kg

Mass Analyzer Miniaturized single quadrupoleIonization Source Chip based electrospray ionizationDetection Range m/z 80–800Mass Accuracy ± m/z 0.5 in full scan in a temperature controlled environment, ±3 °CMass Resolution m/z 0.7 ±0.1 FWHM in full scan in a temperature controlled environment, ±3 °CSampling Adjustment AutomaticStart-up Time 30 minutes*Vacuum Pumps Fully integratedControl Interface Isolera™ SpektraUser Serviceable Parts Spraychip® (chip based ESI source) Vac-chip™ (micro engineered atmospheric pressure interface)

Compatible Systems Isolera™ Spektra Flash Chromatography systems

Gas Requirement 2–6 bar N2

Gas Consumption 2.5 L/minPower Requirement 100–240 V AC; 50–60 Hz


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Biotage Dalton Ordering Information

Part Number DescriptionISO-DALT-NLINK Isolera™ Dalton NanolinkISO-DALT-DET Isolera™ Dalton Mass Detector SER-DALT-IN Isolera™ Dalton InstallationSER-DALT-SAP Service Agreement - Priority - Isolera™

Dalton 413712

Mass Detector Vac-chip 100 (1pcs.)

413711Mass Detector Spraychip 200 (1pcs.)

413874Masscape SW for Personal Computer


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Biotage Dalton Pricing Information

■ Syngenta in Switzerland early 2013 – verbally told 80K

■ University of New Orleans at Spring ACS $110k

■ Flyer in Japan in June $100k

■ BMS in July $115K

■ Anonymous inquiry $115k for complete system $100k for upgrade to existing system


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Competitive Position Against Biotage

TIsco

■ Need external pump so user can choose/switch between ESI and APCI interfaces

Biotage

■ Will stress internal vacuum pump only


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Interchim puriFlash MS

■ Mass triggered fraction collection from normal & reverse phase flash chromatography & prep-LC

■ Mass & Purity confirmation of flash fractions

■ 100% confidence

■ Real-time reaction monitoring of batch reactions

■ The hood-based puriFlash MS reduces the burden on open-access platforms


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Interchim Specifications

■ Ion Source: APCI (ESI as option, easy switch) API: orthogonal ion sampling from heated capillary – allows for small single turbo pump (Patents pending)

Flow rate range: 10 µL/min to 500 µL/min Polarity: +ve and –ve ion in sequential analyses m/z Range: m/z 10 to m/z 1,200Acquisition rate: 5,000 m/z units sec.1

Resolution: 0.5-0.7 m/z units (FWHM) at 1000 m/z units sec-1 over entire acquisition range

SIM sensitivity: 10 pg Reserpine (FIA - 5µL injection at 100 µL/min) 100:1 S/N (RMS) with SIM of m/z 609.28

Scan sensitivity: 100 pg Reserpine (FIA - 5µL injection at 100 µL/min) 100:1 S/N (RMS) with full-scan acquisition of m/z 100 to m/z 1200

Accuracy: +/- 0.1 m/z units over entire acquisition rangeStability: +/- 0.1 m/z units 12 hours in temperature controlled environment (21 +/- 3°C)


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Competitive Position Against Interchim

TIsco■ Standard with ESI, APCI optional

■ Control through PeakTrak

■ Integrated Fluid Interface

■ Should have a price advantage over Interchim

■ Local service support

■ SIMPLE!

Interchim■ Standard with APCI, ESI optional

■ Don’t know how controlled – most likely through a Window’s task screen

■ Screen shots on website show Advion control software

■ No description of fluid interface – believe it to be modular

■ Specifications are just a repeat of the Advion specs


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Agela Cheetah system coupled with cMS

■ We are highly thankful to all our customers who visited our Booth and shown their interest in our products . We will surely address the queries/address of our privileged customers through our Indian office and look forward for business patronage with Indian customers.

■ This was announced at a trade show in India in December 2012.

■ No further information has been seen since.

■ Focus is reportedly on interfacing with their Flexa HPLC system


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Accessories/Upgrades

Part Number

List Price

68-5237-050 PurIon Including Fluid Interface $68,484

68-5237-081 Fluid Interface $18,543

68-5237-051 CombiFlash Rf Upgrade including PurIon $70,146

APCI Ionization Probe Option

Roughing Pump Vent Kit

Demo Kit for MS


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Roughing Pump Vent Kit


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Wednesday August 28 Agenda Group 1 Group 2

800 AM Lab III Lecture III

Operation CombiFlash Rf + Details CombiFlash Rf 150

1000 AM Break Break

1030 AM Lab IV Lecture IV Torrent Columns and Column Plan

Troubleshooting

1200 PM Lunch Lunch

130 PM Lecture III Lab III

Operation

230 PM Break Break

300 PM Lecture IV Lab IV

Troubleshooting


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Key Markets

PharmaceuticalDrug Discovery Natural

Products

AgriculturalChemistry Foods

and Flavors

Petrochemicals

overview of combiflash product line teledyne isco confidential 1

Documents

overview combiflash

combiflash rf purion

combiflash rf uv ms

combiflash rf uvvis

current products rf

redisep rf gold media

flash detectors uv

ms vendor