Impact of Collaborative Robots at The Genomics Institute of the Novartis Research Foundation (GNF) Dan Sipes Novartis Foundation

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1 Impact of Collaborative Robots at The Genomics Institute of the Novartis Research Foundation (GNF) Dan Sipes Novartis Foundation

2 Outline What is GNF? Approach How it works The need for collaborative robots

3 What is GNF? History: Genomics technology & basic research drug discovery People: Scientists and engineers with multi-disciplinary expertise Organization: Distinct structure, culture and operating model Purpose: Catalyze and advance new ideas within NIBR

4 Salk Scripps UCSD Sanford- Burnham Pfizer J&J

5 Outline What is GNF? Approach How it works The need for collaborative robots

6 GNF Discovery Paradigm Fundamental Biology GNF Technology Novel Assays and Assay Systems GNF Technology Innovative Drugs and Drug Targets

7 Diversity of Screening at GNF Disease Biology Target Driven Surface Receptors Ion Channels Enzymes Transcription Factors Protein Protein Interactions Phenotypic Cell function Viability & Proliferation Differentiation Morphology Infection (Whole organism) GNF automation Screening Format Biochemical Protein Binding Enzyme Activity FRET Functional Protein Expression Receptor Activation Agonsim and Antagonism Cellular Protein localisation Cell Cycle & Division Imaging Flow Cytometry Whole Organism

8 Outline What is GNF? Approach How it works The need for collaborative robots

9 Examples of GNF Technology Platforms High-Throughput Compound Screening Automated genomic profiling Protein and Antibody Engineering Automated Cell/Compound Profiling High-Content Imaging Informatics Protein X-ray Structure Determination Secretomics Automated Protein Production and Purification

10 GNF Engineering Enables Breakthrough Biology uhts ACP Capabilities Fully automated screening: >2 million compounds in a week Fully automated screening of genomics libraries (cdna, sirna, shrna, etc.) Automated protein expression, purification and analysis AGS Complex assays High-content imaging Three-dimensional assays Synergy screening Live pathogen (parasites, fungi, bacteria) screening uhts: Ultra-High-Throughput Screening ACP: Automated Cell Profiling AGS: Automated Genomic Screening

11 GNF HTFCM Screening System Climate controlled incubators: Space for 972 assay plates. Climate controls include temperature, humidity, CO 2. Random access to plates and flasks. Spin/seal/peel workflows: Facile movement of plates on/off system. Centrifuge allows extensive processing of suspension cells. FACS sampler: Rapidly and reliably moves sample from plate to FACS. Speed, sampling time, wash steps all programmable. Beckman Coulter CyAn: Fast, reliable three-laser system. Chilled incubators: Store delicate samples as well as allow advanced assay methods such as receptor internalization. WDII: Advanced features allow gentle processing of delicate cells during complex dispense/aspirate routines. Agilent Bravo pipettor with stackers: Supernatant transfers, plate compressions, etc. with either tip-washing or tip-changing.

12 GNF HTS System

13 GNF HTS System in Action

14 Outline What is GNF? Approach How it works The need for collaborative robots

15 R&D Infrastructure Potential for seamless transition from idea to the clinic and beyond Technology Initiatives Antibody-Drug Conjugates, Secretomics, Genetics, Genomics Core Areas of Biology Oncology, Metabolism, Immune Regulation, Infectious Disease, Regenerative Medicine Drug Discovery Pipeline LMW and biologics infrastructure Broadly-enabling technology platforms Development Candidates Diversity of Approach Pathway- and Target-based Screens, Cell Therapy Academic & Cross-NIBR Collaborations

16 The Need for Collaborative Robots/Small Systems Many reasons Assay development for HTS Follow-up on hits Small screens Workstations optimized for interaction with bench scientists Without small systems we receive requests to run small screens online Assays benefit from automation Large systems optimized for large-scale high throughput simple assays Small requests can have big impact - medchem Small systems will allow scientists to rapidly and consistently run assays in a timely fashion without interrupting online operations

17 Impact of Collaborative Robots at GNF Puts power of automation into hands of scientists Increased walk-away, repeatability and rigid timing with data logging better data quality vs. manual Enables scientists to expand assay development windows (explore additional parameters, such as timing, in more depth) which will result in higher quality hits/leads Highly configurable systems maximize functionality while minimizing footprint. Can easily adapt to evolving lab environment. Encourages scientists to better understand the technologies which enable their research

18 Requirements for Collaborative Robots at GNF Easily configurable/re-configurable Integrate common lab devices and HTS components Small footprint Designed with the bench scientist operator in mind Safe and easy access ( cage-free - no hard guarding or light curtains)

19 Smaller Systems at GNF Offline Workstations

20 High Content Imaging Workstation Commercial scheduling software Imager Four axis robot FILO plate storage Barcode reader Next: automated incubator and washer/dispenser

21 Summary of Collaborative Robotics at GNF Requires significant upfront investment Long term payback Enabled science across domain expertise Technology platforms benefit through rapid deployment, increased productivity and superior support and service Critical mass of systems required for maximum benefit

22 Acknowledgments San Diego, CA Novartis Institutes for BioMedical Research (NIBR) locations