1. Overview of CombiFlash Product Line
Teledyne Isco Confidential

2. Teledyne Isco Confidential
Agenda
Overview
Product Availability Dates
Pricing
Phase out of Current Products
Detailed Description of CombiFlash Rf+ PurIon
Teledyne Isco Confidential

3. Teledyne Isco Confidential
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
Teledyne Isco Confidential

4. Product Availability Dates
CombiFlash Rf+
CombiFlash Rf+ Lumen
CombiFlash Rf+ PurIon
Available for customer shipment by October 31st
CE Mark by October 31st
Teledyne Isco Confidential

5. Teledyne Isco Confidential
Pricing
CombiFlash Rf+ UV
$30,327
CombiFlash Rf+ UV/Vis
$31,269
CombiFlash Rf+ UV MS Ready
$31,587
CombiFlash Rf+ UV/Vis MS Ready
$32,529
CombiFlash Rf Lumen UV
$45,930
CombiFlash Rf Lumen UV/Vis
$47,236
CombiFlash Rf Lumen UV MS Ready
$47,190
CombiFlash Rf Lumen UV/Vis MS Ready
$48,496
CombiFlash Rf PurIon UV
$98,286
CombiFlash Rf PurIon UV/Vis
$99,167
CombiFlash Rf PurIon UV with ELSD
$118,462
CombiFlash Rf PurIon UV/Vis with ELSD
$119,348
Teledyne Isco Confidential

6. Phase Out of Current Products
Rf 200 and Rf 200i modules will be shipped until the end of December
, , , and
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
Teledyne Isco Confidential

7. Introducing the CombiFlash Rf+ PurIon
A Fully Integrated
Flash Chromatography – Mass Spectrometer System
Teledyne Isco Confidential

8. Teledyne Isco Confidential
Topics
The Question
Partner
How Does it Work
Functions
Control
Competition
Accessories
Teledyne Isco Confidential

9. Teledyne Isco Confidential
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.
Teledyne Isco Confidential

10. 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
Teledyne Isco Confidential

11. Teledyne Isco Confidential
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
Teledyne Isco Confidential

12. Teledyne Isco Confidential
Advion
Global Headquarters
Ithaca, New York
A Leader of Mass Spec and Microfluidic Systems based upon decades of LC/MS expertise
Teledyne Isco Confidential

13. Teledyne Isco Confidential
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)
Teledyne Isco Confidential

14. Teledyne Isco Confidential
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
Teledyne Isco Confidential

15. Teledyne Isco Confidential
What is different about Advion’s expression Compact MS?
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
Teledyne Isco Confidential

16. Teledyne Isco Confidential
Specifications for CMS – not PurIon
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 sec1 (compatible with UPLC)
Resolution: m/z units (FWHM) at 1000 m/z units sec1 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
Accuracy:  0.1 m/z units over entire acquisition range
Teledyne Isco Confidential

17. Components making up a CombiFlash Rf+ PurIon
CombiFlash PurIon Detector Module
Fluid Interface
Roughing Pump
Teledyne Isco Confidential

18. Fluid Interface Flow Diagram
Pulse damper
Pressure Transducer
To Mass Spec
Splitter
Valve
Prime valve
Back pressure
40 psi
From Rf port C
To Rf port D
Pump head
Teledyne Isco Confidential

19. Method Development to Ion Source
From
Fluid
Interface
2 µm
Filter
Method
Development
Inject Valve
Ion
Source
Teledyne Isco Confidential

20. Teledyne Isco Confidential
Under the Cover View
Prime Valve
Pressure
Transducer
Carrier Pump
Pulse Damper
Back Pressure Regulator
MRA (Splitter Valve)
Teledyne Isco Confidential

21. Front and Back Panels of Fluid Interface
Power Cables for MS and Rf
Prime Valve
USB to Rf
Carrier Pump
MRA
USB from front of MS
USB to back of MS
AC Power Cord
Teledyne Isco Confidential

22. Teledyne Isco Confidential
Functions/Options
Target Mass or Mass Range Detection
ESI or APCI
Positive or Negative Ionization
Pre-purification verification
Reaction Monitoring
Teledyne Isco Confidential

23. Teledyne Isco Confidential
Control
Single point control via PeakTrak
User does not have access to all operating parameters
Goal was to keep operation SIMPLE
Teledyne Isco Confidential

24. Teledyne Isco Confidential
MS Settings
Teledyne Isco Confidential

25. Method Development Screen
Pre-purification Verification
Reaction Monitoring
Flow Injection Analysis
Teledyne Isco Confidential

26. Flow Injection or Reaction Monitoring
200 µL/min
to ESI/APCI Mass Spectrometer
CombiFlash Rf+
Return to UV
Column
mL/min Gradient
Isocratic make up Pump
Rheodyne Mass Rate Attenuator (MRA)
200 µL/min Methanol with 0.1% Formic Acid
Teledyne Isco Confidential

27. Manual Injection Valve
Port
Drain
Tube
To Ion
Source
From
Fluid
Interface
Scan Mass
Position
Inject Sample
Position
5 µl volume
tubing
Teledyne Isco Confidential

28. Teledyne Isco Confidential
MS Tab Options
Teledyne Isco Confidential

29. Teledyne Isco Confidential
Manual Control
Teledyne Isco Confidential

30. Teledyne Isco Confidential
Real Time Run Display
Teledyne Isco Confidential

31. Past Peak MS Display in Real Time
Teledyne Isco Confidential

32. Teledyne Isco Confidential

33. Teledyne Isco Confidential
Post Run MS
Teledyne Isco Confidential

34. CombiFlash Rf+ PurIon Specifications
Dimensions (W x H x D) CombiFlash PurIon Mass Detector: cm Fluid Interface cm CombiFlash Rf+ PurIon system: cm
Roughing Pump:
Weight CombiFlash PurIon Mass Detector: kg Fluid Interface: kg CombiFlash Rf+: kg
Roughing Pump: CombiFlash Rf+ PurIon system: kg
Mass Analyzer Single quadrupole
Ionization Source Electrospray ionization (Optional Atmospheric Chemical Ionization)
Detection Range m/z 50 – 1200
Mass Accuracy ± m/z 0.5 in full scan in a temperature controlled environment, ±3 °C
Mass Resolution m/z ± 1
Sampling Adjustment Automatic
Start-up Time minutes after roughing pump reaching full vacuum
Vacuum Pumps Integrated Turbo pump, external roughing pump
Control Interface PeakTrak
Compatible Systems CombiFlash Rf+ and CombiFlash Rf+ Lumen (Mass Ready) Systems
Upgraded CombiFlash Rf200 Systems
Gas Requirement bar N2
Gas Consumption 4 L/min
Power Requirement –240 V AC; 50–60 Hz
Teledyne Isco Confidential

35. Teledyne Isco Confidential
Typical Messages
Teledyne Isco Confidential

36. Teledyne Isco Confidential
Typical Messages
Teledyne Isco Confidential

37. Going from Standby to Operate
Teledyne Isco Confidential

38. Going from Operate to Standby
Teledyne Isco Confidential

39. Teledyne Isco Confidential

40. Teledyne Isco Confidential
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
Teledyne Isco Confidential

41. Biotage Isolera Dalton
Flash Chromatography with Integrated Mass Identification
Be 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.
Teledyne Isco Confidential

42. Teledyne Isco Confidential
Biotage Claims 1
Biotage
TIsco
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.
Teledyne Isco Confidential

43. Teledyne Isco Confidential
Biotage Claims 2
Biotage
TIsco
Tailored Technology Isolera 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. 
PurIon system is not miniaturized and requires an external roughing pump – reduces the possibility of plugging
Teledyne Isco Confidential

44. Teledyne Isco Confidential
Biotage Claims 3
Biotage
TIsco
Intelligent Integration Seamless 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
The Fluid Interface provides control of carrier solvent and switching valve
Teledyne Isco Confidential

45. Teledyne Isco Confidential
Biotage Claims 4
TIsco
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
Requires an external roughing pump – Biotage does not since they do no offer the option of APCI probe
Teledyne Isco Confidential

46. Biotage Dalton Specifications
Dimensions (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 cm Isolera™ Dalton system: 85 x 59 x 62 cm
Weight
Isolera™ Dalton Mass Detector: 32 kg Isolera™ Dalton Nanolink: 10 kg Isolera™: 35 kg Isolera™ Dalton system: 77 kg
Mass Analyzer
Miniaturized single quadrupole
Ionization Source
Chip based electrospray ionization
Detection Range
m/z 80–800
Mass Accuracy
± m/z 0.5 in full scan in a temperature controlled environment, ±3 °C
Mass Resolution
m/z 0.7 ±0.1 FWHM in full scan in a temperature controlled environment, ±3 °C
Sampling Adjustment
Automatic
Start-up Time
30 minutes*
Vacuum Pumps
Fully integrated
Control Interface
Isolera™ Spektra
User 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/min
Power Requirement
100–240 V AC; 50–60 Hz
Teledyne Isco Confidential

47. Biotage Dalton Ordering Information
Part Number
Description
ISO-DALT-NLINK   
Isolera™ Dalton Nanolink
ISO-DALT-DET
Isolera™ Dalton Mass Detector 
SER-DALT-IN 
Isolera™ Dalton Installation
SER-DALT-SAP
Service Agreement - Priority - Isolera™ Dalton 
413712
Mass Detector Vac-chip 100 (1pcs.)
413711
Mass Detector Spraychip 200 (1pcs.)
413874
Masscape SW for Personal Computer
Teledyne Isco Confidential

48. 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
Teledyne Isco Confidential

49. Competitive Position Against Biotage
TIsco
Biotage
Need external pump so user can choose/switch between ESI and APCI interfaces
Will stress internal vacuum pump only
Teledyne Isco Confidential

50. 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  
Teledyne Isco Confidential

51. 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 1,200 Acquisition rate: 5,000 m/z units sec.1  Resolution:  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 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 Accuracy: +/- 0.1 m/z units over entire acquisition range Stability: +/- 0.1 m/z units 12 hours in temperature controlled environment (21 +/- 3°C)
Teledyne Isco Confidential

52. Competitive Position Against Interchim
TIsco
Interchim
Standard with ESI, APCI optional
Control through PeakTrak
Integrated Fluid Interface
Should have a price advantage over Interchim
Local service support
SIMPLE!
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
Teledyne Isco Confidential

53. Teledyne Isco Confidential

54. Teledyne Isco Confidential

55. Teledyne Isco Confidential

56. Teledyne Isco Confidential

57. Teledyne Isco Confidential

58. 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
Teledyne Isco Confidential

59. Accessories/Upgrades
Part Number
List Price  
PurIon Including Fluid Interface
$68,484
Fluid Interface
$18,543  
CombiFlash Rf Upgrade including PurIon
$70,146
APCI Ionization Probe Option
Roughing Pump Vent Kit
Demo Kit for MS
Teledyne Isco Confidential

60. Teledyne Isco Confidential
Roughing Pump Vent Kit
Teledyne Isco Confidential

61. Wednesday August 28 Agenda
Group 1
Group 2
800 AM
Lab III
Lecture III
Operation
CombiFlash Rf + Details
CombiFlash Rf 150
1000 AM
Break
1030 AM
Lab IV
Lecture IV
Torrent
Columns and Column Plan
Troubleshooting
1200 PM
Lunch
130 PM
230 PM
300 PM
Teledyne Isco Confidential

62. Key Markets Pharmaceutical Drug Discovery Agricultural Chemistry
Petrochemicals
Natural Products
Foods and Flavors
Teledyne Isco Confidential