1 Right-Sizing Automation for Medicinal Chemistry Support your entire department with One-Minute NMR...

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Right-Sizing Automation for Medicinal ChemistrySupport your entire department withOne-Minute NMRTM

• Fun• Easy• Robust• Fast• Efficient• Economical• Controllable• Flexible

Copyright © 2006 by Protasis Corporation, All Rights Reserved

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Enhancing Your NMR InvestmentGet the most from your instruments

• Easy Open Access Web login for vials and plates reduces time spent in the lab.

• Automated System Suitability and Maintenance provides assurance of good spectra.

• Microgram Samples avoids return trips to the lab and enables scale-down upstream in your workflow.

• Plate and Vial Submission simplifies reformatting and sample preparation.

• Closed-Loop Instrument Control enhances NMR error reporting

• Integrated ACD/Labs and One-Moon Scientific back-end software eliminates manual processing steps.

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Answers Needed From NMR


90%

9% 1%

Did I makethe stuff?What is thisstuff?Other

Source: Survey of 40+ Industry and Academia by Protasis Corporation

Bonus: yield (ERETIC)Percentage Of Samples

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What is it?

Everyone wants a magic wand!

Leap/CTC PALLiquid Handler

CapNMR ProbeNMR Spectrometer

ACD/Automation Server

E-Mail OrWeb Site

You Just Log In Samples

One-Minute NMRManages The Details

ACD/Web Librarian

Did I make it?

Yield?


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UseCapNMR

Log-in Samples…

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Walk away…Let One-Minute NMR run your sample

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Click…

Seconds Later…In your InBox

Hot-linked E-mail reportIntegrated ACD/Web Librarian


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LEAP PAL

• Fast• Low Volume Pickup• Low Dead Volume• Syringe-Only

Technology• Flexible Sample

Storage • Dilute /

Reconstitute• Sample Return


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Effortless Solvent Management

• Vacuum Degasser– Smooth

MicroFlows

• Helium Sparging / Blanketing– Protect

Expensive Deuterated Solvents


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HTSL High-PressurePumping System

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NMR Instrument AutomationYour spectrometer is controlled and Monitored by the One-Minute NMR system.

SEND: • Commands to start experiments• Create sample directories• Query file locations• Molecule files

RECEIVE:• Status messages• Error messages• File locations

You get e-mail:Finished NoticesPlate maps with integrated processing software.Error alerts from NMR, Liquid Handler, etc.

On your Web* site:Main Web PageACD/Labs WebLibrarian

*

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Automated System Suitability• Certified and Sealed standard solutions in

your solvent• Run before every Nth sample or at startup• Checks Signal / Noise and Line Shape to

assure good results. Stops if out of spec.

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ACD/Labs Structure Confirmation and DatabasingAdaptive Experiments Get Results, Save Time

1D Proton

>= 1D Proton Acceptance Level

HSQC

ConfirmedRejected

>= AVG(HSQC + 1H1D) Acceptance Level

YESNO


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Automated System MaintenanceThis is flow

• Probe Clean Every Nth Sample– 1 or 2 cleaning solutions 1 or 2 solvent

flushes– Specially designed Acid + Base solution

• Automated Startup and Shutdown Procedures– 1 or 2 Injector and syringe cleans– Probe cleans– Solvent flushes

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Microgram SamplesMake it easier

• 30 – 300 micrograms of typical small molecules works great

• If that is all you have, then get it returned.• Plenty of source sample, why bother going

back to the lab for 100µg?• Perfect match for analytical (.46cm) scale

HPLC peak, scaled-down your purifications• Or, take 20µL from semi-prep HPLC fraction

exchange to d-solvent

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The Advantages of CapNMR (micro-scale)

Scaled-Down Purifications

Scrape off a spot into filter. Add DMSO-d6, spin.

Collect fractions at analytical scale HPLC

Exchange to minimal d-solvent

A

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The Advantages of CapNMR (micro-scale)

A

Can you spare a few µg? No waiting at the NMR Lab! No return trip!

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The advantages of going tubeless…

•No shimming between samples•No washing tubes

•Minimal sample transfer

•Efficient storage

•Disposable

•Economical

Incredible Time Savings


Plates Make It EasyWould you ever run these in tubes?

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Current One-Minute NMR Installations

• 22 Systems Total• 17 Varian• 5 Bruker• 1 Custom Automated Structure

Confirmation Systems (VNMR)• 2 Turn-Key Automated Structure

Confirmation Systems (VNMR/VNMRJ)

• 3 Walkup Open Access Systems


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Use CasesInterviewed Feb 9, 2006 & Feb 15, 2007

Scientist AMajor PharmaceuticalOpen-Access converted to a service.

Scientist CMajor PharmaceuticalOpen-Access Improvement

A

B


C

Scientist BMajor PharmaceuticalVAST Replacement

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Use Case: Scientist A

A

Before One-Minute NMR

• 3 NMR Systems• 5mm Tubes• Open-Access• Chemists Prepare Samples• Chemists Interpret Spectra• Actual use: 600 samples / month.• Capacity: 1900 samples / month

“If utilization gets to 100% there is a hanging.”


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Use Case: Scientist A2 One-Minute NMR Discovery Tower Systems + ACD/Labs AutomatedStructure Confirmation

• Actual Use: 4000 / month• Capacity: 8000+ / month • Structure Verification for Every Sample• 1D Verification, 60% Accurate• Water Suppression• ERETIC Quantitation

“Different dynamics now: Verification, used to be done by chemists. It is easy with familiar compounds, but hard when chemistry changes. The demand went way up from Parallel Medicinal Chemistry. It puts NMR back in the game for structure verification.”

A


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A

010002000300040005000600070008000

Before * After

Samples / Month

Actual UseCapacity

* 3 Instruments vs. 2

“OMNMR puts NMR back in the game for verification.”


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Before * After

Direct Labor and Utilization

Labor FTEsActual Use

“I just scan the barcode label and click Start.”

A


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M4_1H_MF.esp

7.5 7.0 6.5 6.0 5.5 5.0 4.5 4.0 3.5 3.0 2.5Chemical Shift (ppm)

0

0.1

0.2

0.3

0.4

0.5

0.6

0.7

0.8

0.9

1.0

No

rma

lize

d In

ten

sity

2.160.132.681.611.42

O

O

OH

CH3

M4_1H_MF.esp

6.865 6.860 6.855 6.850 6.845 6.840 6.835 6.830 6.825 6.820 6.815 6.810Chemical Shift (ppm)

0

0.05

0.10

0.15

0.20

0.25

0.30

No

rma

lize

d In

ten

sity

Scientist A – Model Compound

A

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Use Case: Scientist B

B

Before One-Minute NMR: Conventional Flow Injection

“It all depends on what kind of data, quant?, dilute?, viscous?, auto shimming?”

• Capacity: 10800 samples / month!• Actual Use: 1200 – 1500 samples / month.


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• Capacity: 5800* samples / month• Actual use: 1200 – 2500 samples / month• Solvent + Water Suppression• Much more robust than (conventional flow NMR).• 88 wells/plate, 6 minutes per well, 10 hours per plate, 2.5 plates / day.• Using 1/10th solvent, 1/5th sample mass • More sample goes to screening.• OMNMR Enables combinatorial arrays.• Used for structure verification and patent backup• Happy and looking for continued progress

B

“OMNMR is much more robust than my old system. I would not want to go back.With the old flow system or Tubes you just wouldn’t do it”

* Could run faster

1 entry-level One-Minute NMR System

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0

2000

4000

6000

8000

10000

12000

Before * After

Samples / Month

Actual UseCapacity

B


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0

2

4

6

8

10

Before After

Solvent, Sample, Robustness*

Solvent UseSample UseRobustness

B

* Relative values


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Scientist B: Model Compound

test_save

9 8 7 6 5 4 3 2 1 0 -1Chemical Shift (ppm)

0

0.05

0.10

0.15

No

rma

lize

d In

ten

sity

DMSO-d6

2.0

1

2.6

02

.61

2.6

22

.63

3.1

3

3.5

3

6.5

96.6

1

6.9

26

.93

6.9

6

9.1

8O

OH

CH3

B

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Use Case: Scientist C

C

Before One-Minute NMR: 5mm Tube Walkup

“Chemists are a conservative bunch.”

• 400 MHz Varian• Verification Support• Actual Use: All day, 10 minutes / chemist


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C

“We will buy 2 more systems if we can run samples in 5 minutes”.

1. Walkup Plates and Vials 15 min cycle time, Chemists like the system.

2. Excellent data quality3. Proactive Contact: Administrators like the system

but wish it was faster4. After 1 day of effort, 5 minute cycle times achieved5. After 2 more days of effort, 1.5 minute cycle times

achieved6. Management approval for new systems, contingent

on more effective sample preparation.7. Filter vials, filter removal tool, and instructions sent,

testing underway.

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One-Minute NMR EconomicsHow does it fit in?

• NMR provides valuable structure information. Why not have it for every compound?

• One-Minute NMR puts NMR (vs. MS) back in the game for more samples.

• Do you want to run plates, and keep open access too?

• Thinking about a new NMR to expand capacity? Think again!


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Thanks

• One-Minute NMR Collaborators Everywhere

• Scientist A, B, C (You know who you are.)

AB


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Help spread the word!

www.protasis.com508-481-4163

Now NMR is easier and faster

One-Minute NMR

http://www.protasis.com/

1 Right-Sizing Automation for Medicinal Chemistry Support your entire department with One-Minute NMR...

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