Produktivitätswerkzeuge für die NMR

Transcription

1 Produktivitätswerkzeuge für die NMR Till Kühn VP Applications Development Benutzertagung Karlsruhe November 2016 Innovation with Integrity

2 A week in the life of Brian Brian Works in a hypothetical pharma company / university Runs the NMR service lab Is the resident NMR expert in the organization Has a solid NMR background from university

3 At university Academia benefits from Free TopSpin 3.5 processing SW! Download from website

4 Today: The resident NMR expert needs to handle a multitude of tasks and questions New: Experiment Selector Small molecule structure elucidation NMR with labeled proteins Solid state NMR Fragment based drug discovery Brian can t be the expert on everything! He needs help to make the right choices for problem-taylored experiments In TopSpin 3.5

5 New in TopSpin: Experiment Selector Easy access to experiment libraries for all aspects of NMR research Grouping by application area Expandable and easy to personalize Scripted parameter optimization Single click experiment setup - also for multi-receive experiments

6 New in TopSpin: Experiment Selector Easy access to experiment libraries for all aspects of NMR research Parallel HC HMBC and FC HMBC Grouping by application area Expandable and easy to personalize Scripted parameter optimization Single click experiment setup - also for multi-receive experiments Automatic processing etc. possible

7 Work does not stop on weekends automation is key for productivity and load factor on the instrument Nicole needs a fragment based bioaffinity screening project done: 3 x 96 protein samples in buffer Michael wants a quality check for integrity and concentration on a newly synthesized library: 96 samples in DMSO Aisha from development has 5 single samples, she needs the potency/purity Kim has one precious sample where she needs a full structure verification on. She already has the HRAM-MS data

8 New temperature control for SampleJet Individually temperature controlled 5 x 96 rack positions Temperature equilibration station 96 spinner-less open access positions Storage of cold and warm samples at the same time No more need for individual spinners

9 Nicole s Fragment Based Screening Project automation is key for productivity and load factor on the instrument Nicole needs a fragment based bioaffinity screening project done: 3 x 96 protein samples in buffer Chu wants a quality check for integrity and concentration on a newly synthesized library: 96 samples in DMSO Aisha from development has 5 single samples, she needs the potency/purity Kim has one precious sample where she needs a full structure verification on. She already has the HRAM-MS data

10 Nicole s Fragment Based Screening Project For the screen, Nicole has prepared cocktails of protein plus 5 8 ligands in buffer Brian used CMC-q for NMR QC on all ligands In aqueous buffer automatic setup & analysis Nicole tailored her library: she now has good ligands, soluble in buffer with known concentrations Nicole also has all reference spectra! Brian uses the new FBS parameter-sets for the screening November 10,

11 New: FBS data acquisition and analysis November 10,

12 New: FBS data acquisition and analysis November 10,

13 Brian s rest of the weekend automation is key for productivity and load factor on the instrument Nicole needs a fragment based bioaffinity screening project done: 3 x 96 protein samples in buffer Michael wants a quality check for integrity and concentration on a newly synthesized library: 96 samples in DMSO Aisha from development has 5 single samples, she needs the potency/purity Kim has one precious sample where she needs a full structure verification on. She already has the HRAM-MS data

14 Michael s multi sample quality control Brian needs to select the optimal experiments for QC of diverse samples Different concentrations Different structural complexity Different spectra complexity Some DMSO samples will need water suppression Run all samples with a complete set of experiments to ensure optimal data (enough scans, HSQC on everything, maybe even auto water suppression ) not enough time for the other tasks To heck with this, just run the 1D s and let Michael figure it out on Monday (knowing that several spectra will need to be re-run ) Check back on the progress every few hours, look at the results and setup follow-up experiments where needed. IT S THE WEEKEND!

15 The intelligent instrument SmartDriveNMR OK OK Brian SmartDriveNMR requests further experiment Additional data when useful Good quality spectra Higher confidence for auto generated results

16 Michael s multi sample quality control Samples are acquired with optimal and optimized experiments Data is pre-interpreted, for Michael to review in CMC-assist

17 Brian s rest of the weekend automation is key for productivity and load factor on the instrument Nicole needs a fragment based bioaffinity screening project done: 3 x 96 protein samples in buffer Michael wants a quality check for integrity and concentration on a newly synthesized library: 96 samples in DMSO Aisha from development has 5 single samples, she needs the potency/purity Kim has one precious sample where she needs a full structure verification on. She already has the HRAM-MS data

18 New: purity assessment by CMC-assist Aisha needs to know the absolute purity (potency) of some API s Setup in IconNMR Analyte: known compound Potency: 98% Standard: certified refernce material Input: weight of standard & analyte Automatic interpretation with detailed analysis result, for Aisha to review Area** IS Area** analyte Prep. Wt a. [mg] Wt IS [mg] CH Region 1 Region 2 Region 3 Averaged Area a. SD Area a. Potency [%] RSD Potency [%] Average

19 Brian s rest of the weekend automation is key for productivity and load factor on the instrument Nicole needs a fragment based bioaffinity screening project done: 3 x 96 protein samples in buffer Michael wants a quality check for integrity and concentration on a newly synthesized library: 96 samples in DMSO Aisha from development has 5 single samples, she needs the potency/purity Kim has one precious sample where she needs a full structure verification on. She already has the HRAM-MS data

20 Kim s full verification She wants to be sure, not to file the wrong structure as a drug candidate Orthogonal data is needed to minimize the chance for false positives MS can do things NMR can not (Cl/Br, S/O ) Nominal mass leaves 1 000s of potential false positives HRAM-MS verifies the molecular formula NMR can do things MS can not 100 s of possible structures per molecular formula 1D 1 H HSQC HMBC 13C Further reduction of potential wrong passes

21 New: Bruker Fusion-SV 1.1 one unified result HRAM-MS and NMR data Details shared projects info in a nutshell

22 Bruker Fusion-SV 1.1: Workbench accurate mass and isotopic pattern information automated analysis and assignment of NMR data

23 New: Bruker Fusion-SV 1.1 Automatic analysis of combined 1D 1 H, HSQC, HMBC and 1D 13 C data for Automatic processing of NUS data (HSQC, HMBC) Spectra interpretation easily understandable 13 C assignment HMBC correlations

24 A week in the life of Brian Brian the resident NMR expert with academic background: free TopSpin processing SW can not be the expert on everything but TopSpin s new Experiment Selector helps to make choices uses the next generation SampleJet temperature control, for combined automation of bio- and chemistry samples runs CMC-q and the new FBS tool for fragment based ligand screening applies SmartDriveNMR which automatically provides his customers with the optimal set of optimized experiments delivers pre-interpreted spectra by CMC-assist, which now also provides potency information against an internal standard acquires NMR data for chemists which they can easily get auto-analyzed along with HRAM-MS by Fusion-SV 1.1.

25 Alavar Gossert, Wolfgang Jahnke, Marcel Blommers, Cesar Fernandez, Paul Erbel Daniel Wyss and Hugh Eaton And many, many of you who take the time to discuss with us! Stefan Jehle, Pavel Kessler, Fabrice Moriaud, Anna Codina, Björn Heitmann, Jochen Klages, Christine Bolliger, Martin Wyser, Markus Lang, Oliver Horlacher, November 10,

26 Innovation with Integrity Thank you for your attention and come see us for demos and discusions Copyright 2011 Bruker Corporation. Corporation. All rights reserved. All rights reserved.

27 A week in the life of Brian Brian the resident NMR expert But, what about all the open access NMR users? Nope! Where are they? Doesn t he have to run off to all the open access labs on the entire site?

28 And that is because of the new, all purpose routine, cryogen free, bench-top, 400MHz high resolution NMR system that could also deliver 600 MHz CryoProbe performance and even delivers HPLC-MS results And it is actually installed at Novartis, Basel!

29 Too good to be true! There must be strings attached! and, that s actually the case not really a string, but rather a tube Lab2Lab a sample tub system Lab2Lab sender Sample buffer Sample router HPLC MS systems NMR systems

30 Researcher submits analysis sample at the lab-bench Sample submitted in standard lab ware (no NMR tube handling etc.) Same interface for NMR or LC-MS Just asks the system the question, like: verify this structure within 15 minutes After minutes, the researcher gets a mail with the results lab2lab scheduling system will select the next available instrument SmartDriveNMR will select and run the optimal experiments for the given time and problem

31 New: Bruker Fusion-SV 1.1 Fully automatic analysis solution for HRAM-MS and NMR structure verification (SV) NMR HRAM-MS structure centered workflow oriented network embedded made for chemists