Introducing AstraZeneca s Global Capability for Acoustic Tubes. Philip Spencer SLAS CM 2017, Berlin 15 th March 2017

Transcription

1 Introducing AstraZeneca s Global Capability for Acoustic Tubes Philip Spencer SLAS CM 2017, Berlin 15 th March 2017

2 Agenda Why is AstraZeneca investing in next generation technology? What are acoustic tubes? What are the impacts of introducing acoustic tubes? Development of innovative solutions with collaborators 2 IMED Biotech Unit I Discovery Sciences

3 Why is AstraZeneca investing in next generation technology? 3 IMED Biotech Unit I Discovery Sciences

4 Hit Identification of the future Drivers for change More targets Genomics revolution Aligning Drug Discovery Virtual screening More compounds in new chemical space Aligning Compound Management Cherry pick any compound for any screen Use knowledge of targets Better target knowledge Structural biology advances Drive the business Reduce cycle times and costs Automated chemistry Faster synthesis in new areas Information rich assays Deliver highest quality screening data to projects Fully automated acoustic platforms 4 IMED Biotech Unit I Discovery Sciences

5 AstraZeneca s new R&D facility at the Cambridge Biomedical Campus 5 IMED Biotech Unit I Discovery Sciences

6 AstraZeneca s new R&D facility at the Cambridge Biomedical Campus March IMED Biotech Unit I Discovery Sciences

7 What are acoustic tubes? 7 IMED Biotech Unit I Discovery Sciences

8 Acoustically-qualified storage tubes What are they? A long-term storage tube for compound solutions that s qualified for use with acoustic dispensing technology What are the benefits? Extremely precise transfer of solutions without contact Reduce compound volumes Miniaturise compound storage What is the impact? Unparalleled quality in screening data 4-fold increase in cherry-picking Reduced compound consumption Distribute all new compounds to all sites Collection sub-sets held locally What are the timelines? Commercial tubes 3Q 2017 Deploy to Cambridge in 2018 Deploy globally in 2019

9 Acoustically-qualified storage tubes 9 IMED Biotech Unit I Discovery Sciences

10 Current state of compound plate preparation 1ml storage tubes Intermediate Plate 10 IMED Biotech Unit I Discovery Sciences

11 Future state of compound plate preparation 85µl storage tubes Working volume 70mL >10-fold reduction in usage 5-fold more storage capacity 24M cherry-picks/year Low volume Intermediate Plate 11 IMED Biotech Unit I Discovery Sciences

12 What are the impacts of introducing acoustic tubes? 12 IMED Biotech Unit I Discovery Sciences

13 Activity % Better quality screening data Fully acoustic workflows will provide Extremely accurate and precise transfer of solutions Eliminate the potential for cross contamination or carryover with contactless transfers Ejection of 2.5nl droplets Log concentration Improved curve fits More accurate potency values

14 Rapid cherry-picking Step change in sample throughput Store more samples in the same space Move more samples in the same time Pick more samples at the same time Maximise uptime Ultra high density storage tray Intelligent tray delivery algorithms Intelligent tube picking algorithms Design for maintenance Small footprint tube Dual tray carrying Quad tray lane picking positions Design for reliability Multiple tray transfer robots Multiple tube picking robots

15 Reduced compound consumption Plate production for cell screening 30µL transfer Conventional dispense Separate control plate = more plate movements Echo dispense Matrix tube Up to 1mL 10mM solution 384-well intermediate plate 20µL dead volume Limited capacity Limited format (quadrants and up to 4 points only) Cell screening plates for screening cascade 2µL transfer Echo dispense Streamlined process Echo dispense Acoustic tube Up to 85mL 10mM solution 1536-well intermediate plate 1mL dead volume Capacity for more compounds and controls No format restriction (position and number of points) Cell screening plates for screening cascade

16 Local availability and replenishment of project samples Eliminate provisioning for project liquids Provisioning Distribution and Replenishment Time consuming Sub-optimal for global working Complex IT Fast Supports global science Simplified IT

17 Increased storage capacity for local availability of collections Enable local science replicate full collections High cost Ultimate flexibility Complex Centralised single collection Lower cost Inflexible Simplified Distributed collections Full collection at UK Centre for Lead Discovery Local science-focus Intermediate cost

18 Development of innovative solutions with collaborators 18 IMED Biotech Unit I Discovery Sciences

19 Collaboration is the key Leverage years of experience with automation and discovery workflows to define requirements Expertise in developing consumables and instruments tailored for acoustic liquid handling Expertise in development of sample stores, sample storage tubes and tube handing instruments Expertise in development of software applications for sample and workflow management 19 IMED Biotech Unit I Discovery Sciences

20 20 Acoustic Microtube Project Deliverables Echo Qualified Acoustic Microtube - 96/per rack - Screw Cap and 2D Barcode - ~70 µl working volume - ~15 µl dead volume Echo Liquid Handler for Transfer from Tubes - Capable of 555 transfer speed - Will support Screening and Omics calibration sets - Will support transfer from microplates Access Workstations for Processing Tubes and Plates - Dual Echo, dual robot base system - Integration of devices for capping, peeling, sealing, spinning, dispensing, labeling storage and detection - Advanced integration with LIMS to support order management across multiple workstations

21 Echo Acoustic LIQUID HANDLING The Future of Science is Sound Echo Qualified Acoustic Microtube

22 Task 1: DMSO Concentration Measurement Successfully read DMSO concentrations across multiple racks of 96 tubes same signature Validated both with and without a barcode Black Acoustic Tube Expected %DMSO 70% 75% 80% 100% Average 71.08% 75.24% % 99.56% CV 0.90% 0.91% 1.07% 0.27% Black Acoustic Barcoded Expected %DMSO 70% 80% 90% 100% Average 70.98% 79.08% 90.12% 98.55% CV 1.08% 2.48% 1.37% 1.26% 22

23 Task 2: Acoustic Transfer with Barcoded Tubes Successful acoustic transfer at all DMSO concentrations Concentration Volume (nl) CV 100% % 95% % 90% % 85% % 80% % 75% % 70% % 23

24 Task 2: Acoustic Transfer with Barcoded Tubes (100% DMSO) Successful transfer at all fill heights Fill Volume Fill Height Volume (nl) CV 15 µl 0.96 mm % 45 µl 2.85 mm % 95 µl 5.53 mm % 24

25 Echo Acoustic LIQUID HANDLING The Future of Science is Sound Access Workstation for Sample Management

26 Access Workstation Overview Welded steel frames - Common cart bases - Adjustable shelves for devices Docking Echo and device carts Removable doors/panels - Safety interlocks Windows for high visibility Turntables and sliding shelves Drop-down utilities to center cell - Power, air, vacuum, environment Electrical boxes located in robot cells 26

27 27 Access Workstation Overview

28 28 Cells & Carts

29 Improved Integration with Tempo Software Better communication across software applications - Information from Echo system and other devices will be directly accessible to Titian Software No need to track down report files - Echo protocol values will be exposed and directly editable by Titian Software Fewer Echo software protocols to manage System performance tracking - Device and consumable (seal, peel) utilization will be tracked Avoid running out of materials Align preventative maintenance with device utilization Run management - Ability to reprioritize orders and associated runs - Automatically adjust to offline devices (in repair, or standalone use) - 29

30 Brooks and Labcyte Acoustic Tube Application 4 major components for development: New Labcyte Echo Qualified Acoustic Sample Storage Tube 2D barcode Reader (stand-alone and Store Integrated) Capper/Decapper Device New High Density High Throughput Automated Sample Store CONFIDENTIAL 30

31 Technical Challenges Tube Geometry Master Tube: 70ul Working Volume at liquid column height of 5.5mm height (Acoustic Compatible) Internal screw cap with TPE co-molded gasket DEAD VOLUME: mm WORKING VOLUME: - 70 Optimised Tube Geometry for Acoustic Secure Rack for sample handling with Acoustic Dispenser and traditional liquid handlers CONFIDENTIAL 31

32 Technical Challenges Tube Geometry Internal rectangular profile for improved Acoustic performance External round profile for compatibility with Screw Cap Features to prevent tube rotation during picking CONFIDENTIAL 32

33 Technical Challenges Rack Tolerances Need to achieve Tolerances in excess of SBS standards Max Tube to Tube positioning tolerance of less than 175µm Incorporate stress relief features into rack Rack molded from COC (cycloolefin copolymer) CONFIDENTIAL 33

34 Technical Challenges 2D Barcode Placement Acoustic Window Centre portion of tube base needs to be kept clear to avoid interference with Acoustic Dispensing (3mm diameter window) Does not leave enough real estate for a single 2D barcode 2D4 Quad Code Split the 2D unique identifier into 2 smaller codes Software reads 2 of the small codes at the diagonal and are concatenated to make a single code, Code is duplicated for added security add redundancy. A+D= Make one complete code B+C= Duplicate of A+D Code for redundancy An example code would be FR CONFIDENTIAL 34

35 Technical Challenges 2D Barcode Placement 2D4 Perception Rack Reader 2D4 Store Rack Imager / Reader CONFIDENTIAL 35

36 Technical Challenges Cap Design Internal Thread Design to Maximise internal working volume and flight path TPE Gasket for DMSO compatibility and reduced sample loss through evaporation Co-molded design Optimised design for automated decapping / capping Target Increase life cycle from 15 capping cycles to over 500 cycles CONFIDENTIAL 36

37 Technical Challenges Automated Decapper A New Automated Decapper required to provide a consistent torque to each cap in order to prolong the life of the cap (immortalise the sample) and maximise sample integrity 96 Individual electronically controlled motors Interchangeable Cap Drivers (cassette mechanism) Increased speed to shorter cycle time 45s to 30s Improved Integration capabilities Electronic Torque Control Improved GUI Interface Higher duty cycle Modular Design Smaller footprint CONFIDENTIAL 37

38 Technical Challenges How Do You Pick 20 million Samples Per Year? 8 million/yr 20 million/yr 2018 CONFIDENTIAL

39 Technical Challenges SD Tray 576 Tubes per Tray 6 SBS Racks Small footprint tube Ultra high density storage tray Store more samples in the same space HD Tray 1,008 Tubes per Tray New UHD tray 1,280 Acoustic tubes 122% Increase over SBS Racks 27% increase over HD tray CONFIDENTIAL 39

40 Technical Challenges Pick more samples at the same time High Speed Multi Tube Selector Fourth tray lane permits support for multiple order processing and continuous picking 2 positions for UHD store trays 2 positions for (SBS) I/O trays Multiple Tube Picker (3 tubes at a time) Intelligent tube picking algorithms Quad tray lane picking positions Multiple tube picking robots CONFIDENTIAL 40

41 Technical Challenges Dual Shuttle Robot Each Shuttle moves 2 trays (up to 2,560 Acoustic Tubes) 2 Shuttles for double the capacity (up to 5,120 Acoustic Tubes) Multiple Input / Output Modules and Imagers Multiple 4 Lane Picker Provides redundancy during routine maintenance 2 positions for (SBS) I/O trays Move more samples at the same time Intelligent tube picking algorithms Dual tray carrying capability Multiple tray transfer robots CONFIDENTIAL 41

42 Tubes are taken from Store Titian has had an interface between Mosaic and the Brooks SampleStore for many years using the Strata API, and this has kept the risk to this side of the project low. A few enhancements were necessary to support the large number of cherry-picks combined with batching, to increase efficiency between store and Labcyte Access systems. Inventory Data Machine Specific low-level Driver Workflow Data Generic store manager TITIAN-MKTG Feb 2017

43 Labcyte Access Tempo Fulfilment Module A brand new, dedicated client application is currently under development which will streamline the creation of Echo protocols and the initiation of Tempo runs Using a small set of pre-configured Echo protocols, the dose response or cherry pick requirements specified will be translated directly into Tempo protocols Guided direction for operators on batch processing of plates, controls and standards, and then instigating efficient fulfilment within a Tempo run TITIAN-MKTG Feb 2017

44 Thank you 44 IMED Biotech Unit I Discovery Sciences