FAU College of Engineering Seminar - Robotics and Laboratory Automation at Scripps Florida

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Robotics and Laboratory Automation at Scripps Florida

Pierre Baillargeon

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About Scripps Florida

The Scripps Research Institute 2014 All rights reserved

Introduction to drug discovery, robotics and laboratory automation at Scripps Florida

Case study: the development of a novel machine vision instrument

Lessons learned along the way

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Integrated Assay Development, uHTS and Compound Management>982K Compound Screening Collection >622K Proprietary (largest in academia, ~30k unique compounds, focused sub-libraries, professionally curated) >360K Public Domain (NIH)The Lead Identification Laboratories at Scripps


Where robotics, chemistry and biology join forces to help discover new drugs Located in Jupiter, FL >200 targets screened in over 235 robotic experiment campaigns to generate more than 80 million data points for academic & industrial collaborators Multiple Sclerosis (S1P1) drug candidate entered phase 2/3 clinical trials in October 2012

3Assay development Biologists miniaturizing experiments to run on robotic platformsuHTS ultra High Throughput Screening - Robotics Engineers running the robotic experimentation platformsCompound Management Robotics Engineers preparing compounds for testing on robotics platforms

Introduction to Drug Discovery


Average time to develop a new medicine = 10-15 years

4Starting from 600k or 300k, compounds are tested an hits (the compounds that produce the strongest desired endpoint result), are whittled down to a handful of structures which then enter clinical trials



How can we shrink the timeline and reduce the cost of drug discovery?

5(2012 estimate is now at $1.8B)



Using laboratory automation reduces unit cost & increases throughput

1 experiment per test tubeUp to 1,536 experiments per microtiter plate

6Start with empty plate, add assay materials (cells, enzymes, detection reagents, etc.), add compounds to each well, examine each well for result, results stored in corporate database



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Multichannel pipettingBulk reagent dispensingResult Detection & Reporting

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Introduction to Drug DiscoveryThe Scripps Research Institute 2014 All rights reserved

Software automation plays a large role in increased efficiency and quality control

1st generationNo automation2nd generationSoftware automation3rd generationSoftware automation + hardware automation

9Software development, database administration and systems integration play a large part of modern Drug Discovery operations

Example of a typical process at Scripps


COMPOUND SUBMISSIONHas the correct sample been put into the labware?Is the volume and concentration of the sample accurately recorded?

COMPOUND PROCESSINGHas the sample store delivered the correct samples?Has the liquid handling automation pipetted the samples properly?Has the plate been registered correctly?Is the sample itself of high quality?

COMPOUND DELIVERYDo we have a record of what we are delivering?

Room for improvement! How can we QC samples more efficiently?

10This example shows that we are using both software and hardware automation to increase efficiency and improve the quality of the work we are doing

Issues With Compound Libraries


Introduction to drug discovery, robotics and laboratory automation at Scripps Florida

Case study: the development of a novel machine vision instrument

Lessons learned along the way

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Are empty/partially filled wells in Quadrant 1?

Do these wells contain precipitate?My db says this well is empty. Does it actually have sample in it?

Why Do We Need Plate Auditor?


Like a game of battleship12

Should these wells really be empty? What does my database say?

Do these wells contain precipitate?Are these wells partially filled?My experiment is sensitive to purple compounds-where are they?Issues With Compound LibrariesThe Scripps Research Institute 2014 All rights reserved

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What is Plate Auditor? A custom HTS plate reader, incorporating recent advances in machine vision, image analysis, & the spectroscopy sciences

It saves labor by automatically identifying & annotating issues specific to compound libraries:

Colored compounds Precipitate / Crystallization Low volume / Full wells

It can be used in stand-alone mode, or integrated with automation

Works with microtiter plates

Fast: reads a 384 well plate in

Education

FAU College of Engineering Seminar - Robotics and Laboratory Automation at Scripps Florida