An Interactive Automation Experience – Oncology … · An Interactive Automation Experience ......

An Interactive Automation Experience –

Tami Hood

pOncology Cellular Assay Platform ( )

Tami HoodViraj Tyagi

Agilent Users Group Meeting, 2011

2

Roadmap

Who are we? What do we do?

Original Challenges/Oncology needs


Original Challenges/Oncology needsOriginal Challenges/Oncology needs

Project scope/features

Approach



Approachpp

OCAP system details

Using the OCAP system

pp

OCAP system details


OCAP Challenges

Assays

OCAP Challenges

Assays

Potential Improvements

Outlook


Outlook

SuggestionsSuggestions

3

Where?

Novartis Institute of Biomedical Research – Cambridge, MANovartis Institute of Biomedical Research – Cambridge, MA

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Who? What?

Cellular Assays Team – OncologyCellular Assays Team – Oncology

Automate and streamline discovery of structure-activity relationships (SAR) using primary assaysAutomate and streamline discovery of structure-activity relationships (SAR) using primary assays

Project support for different targets

Automation consultation/support

Project support for different targets

Automation consultation/supportAutomation consultation/support

High-throughput data integration and analysis

Automation consultation/support

High-throughput data integration and analysis

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Why?

Novartis: We want to discover, develop and successfully market innovative products to prevent and cure diseases to

Novartis: We want to discover, develop and successfully market innovative products to prevent and cure diseases tomarket innovative products to prevent and cure diseases, to ease suffering and to enhance the quality of life. We also want

to provide a shareholder return that reflects outstanding

market innovative products to prevent and cure diseases, to ease suffering and to enhance the quality of life. We also want

to provide a shareholder return that reflects outstanding performance and to adequately reward those who invest

ideas and work in our company.performance and to adequately reward those who invest

ideas and work in our company.

Novartis Oncology: CURE CANCER!

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Roadmap






Approach



Approachpp

OCAP system details


pp

OCAP system details


Challenges

Assays

Challenges

Assays


Outlook


Outlook


7

Original challenges at Novartis Onc

All assays were in 96-well format (at best)All assays were in 96-well format (at best)

All dispensing was being done manually

Lack of trust in automated solutions

All dispensing was being done manually

Lack of trust in automated solutionsLack of trust in automated solutions

Fear that automation would take away jobs

Lack of trust in automated solutions

Fear that automation would take away jobs

Space constraints

Lack of equipment sharing

Space constraints

Lack of equipment sharing

“21st century science, 20th century technology” - Viraj“21st century science, 20th century technology” - Viraj

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Oncology-specific needs

SAR for small-molecule projectsP i

SAR for small-molecule projectsP i• Primary

• Counter-screens• Secondary assays

• Primary• Counter-screens• Secondary assaysSecondary assays

Validation confirmation

Secondary assays

Validation confirmation

Exploratory screens

Biologics support

Exploratory screens

Biologics support

Automation support for assay development and automationAutomation support for assay development and automation

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Project Scope/Goals

Growing need for higher throughput and efficient assays more data for multiple target based projects

Growing need for higher throughput and efficient assays more data for multiple target based projectsmore data for multiple target-based projects

Desire for ONE system for seeding cells, dispensing reagents treating with compounds ambient/37C storage

more data for multiple target-based projects

Desire for ONE system for seeding cells, dispensing reagents treating with compounds ambient/37C storagereagents, treating with compounds, ambient/37C storage, labeling, and plate reading capabilities

Walk-up and easy-to-use system for numerous associates

reagents, treating with compounds, ambient/37C storage, labeling, and plate reading capabilities

Walk-up and easy-to-use system for numerous associatesWalk-up and easy-to-use system for numerous associates• Ownership

Offline use capabilities

Walk-up and easy-to-use system for numerous associates• Ownership

Offline use capabilitiesOffline use capabilitiesOffline use capabilities

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Specific features desired

Flexible systemFlexible system

Safe, easy-to-use for users with varying automation backgroundsSafe, easy-to-use for users with varying automation backgrounds

User friendly interface

Compact footprint

User friendly interface

Compact footprintMarty

p p

Cost-effective (You listening Marty? Brian?)

p p

Cost-effective (You listening Marty? Brian?)

Most important: A vendor invested in our project, encompassing the care and concern we have for the ultimate customer: the patient!

Most important: A vendor invested in our project, encompassing the care and concern we have for the ultimate customer: the patient!pp

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Roadmap






Approach



Approachpp

OCAP system details


pp

OCAP system details


Challenges

Assays

Challenges

Assays


Outlook


Outlook


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Unique approach

Classical Automation InDaHood approachLarge screening efforts (mostly single

point data)More automation of the routine daily

time-consuming tasksHit confirmation Multiple, simultaneous assays (low to

medium throughput in any data orientation)

Focused screens Shared resources (Open Access)One automation system = One assay Systems that can multi-task and run

overnight, unsupervisedStand-alone use and semi-modular

t tstrategyMultiple users

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Vendors... Potential partners

Considered 4 vendorsConsidered 4 vendors

Desired:• Superior technology, design

Desired:• Superior technology, design• Commitment to excellence• Customer focus• Quick response

• Commitment to excellence• Customer focus• Quick response• Quick response• Outstanding service and applications partnering• Safety measures

• Quick response• Outstanding service and applications partnering• Safety measures• Reputation• Cost

P t l ti hi

• Reputation• Cost

P t l ti hi• Partner relationship• Partner relationship

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Roadmap






Approach



Approachpp

OCAP system details


pp

OCAP system details


Challenges

Assays

Challenges

Assays


Outlook


Outlook


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OCAP - Phase I

“The intern”

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Sample workflow

System setup “Cell seeding” protocol

Compound transfer

Place plates back

in hub “Add reagent”

protocolPlate read -

Envision(incubator)

protocolEnvision

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OCAP Manual (non-OCAP)

OCAP - Phase II

Envision VCode

BravoATS 100ATS 100

Plate Hub

EL406

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OCAP - Phase II

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Phase I vs. Phase II

Phase I Phase IIDDR robotic arm ATS 100 (Acoustic Transfer System)

Envision w/TRF laser Bravo Liquid HandlerEL406 Plate Washer/Dispenser VCode Barcode LabelerEL406 Plate Washer/Dispenser VCode Barcode Labeler

Liconic Steam Injected Incubator Plate Barcode ReaderAmbient Plate Hotel (Plate Hub) 3 docking tables

Liddi /D liddi t tiLidding/De-lidding station

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Sample workflow w/Phase II

System setup “Cell seeding” protocol

Compound transfer

Place plates back

in hub “Add reagent”

protocolPlate read -

Envision(incubator)

protocolEnvision

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OCAP Manual (non-OCAP)

OCAP in action

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OCAP Phase III and other additions

Phase III expansion still under considerationPhase III expansion still under consideration

Potential additions• EL406 for seeding multiple cell lines

Potential additions• EL406 for seeding multiple cell lines• Incubator• InCell (currently stand-alone)• Incubator• InCell (currently stand-alone)

Non-Biocel additions• Cell seeding/plate reading station with Benchbot

Non-Biocel additions• Cell seeding/plate reading station with Benchbot• InCell-Robot integration• InCell-Robot integration

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Using the OCAP system, part I

Consultation visit with the scientistA t

Consultation visit with the scientistA t• Assay type

• Format• Throughput

• Assay type• Format• Throughput• Media (plate, tips, etc)• Future scope• Media (plate, tips, etc)• Future scope

Protocol development (VWorks, etc..)• Testing• Troubleshooting

Protocol development (VWorks, etc..)• Testing• Troubleshootingg

Inaugural protocol run with the scientist• Minor software/hardware training

g

Inaugural protocol run with the scientist• Minor software/hardware traininggg

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Using the OCAP system, part II

2nd run with the scientistS i ti t t k h d t l

2nd run with the scientistS i ti t t k h d t l• Scientist takes hands-on control

Scientist responsible for running the assay• Available for further help teaching training and troubleshooting

• Scientist takes hands-on control

Scientist responsible for running the assay• Available for further help teaching training and troubleshooting• Available for further help, teaching, training, and troubleshooting• Continued support• Once scientist is comfortable running the assay, additional meetings to

f th th ll b ti di i ti th d t k l

• Available for further help, teaching, training, and troubleshooting• Continued support• Once scientist is comfortable running the assay, additional meetings to

f th th ll b ti di i ti th d t k lfurther the collaboration or discuss innovative methods take place

Our role: Facilitators

further the collaboration or discuss innovative methods take place

Our role: Facilitators

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Roadmap






Approach



Approachpp

OCAP system details


pp

OCAP system details


Challenges

Assays

Challenges

Assays


Outlook


Outlook


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Challenges – Multiple users on system

CommunicationC l d b ki t Sh P i t

CommunicationC l d b ki t Sh P i t• Calendar booking system on SharePoint• Calendar booking system on SharePoint

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Challenges – Multiple users on system

Multiple, simultaneous runsS i ti t 1 ll di

Multiple, simultaneous runsS i ti t 1 ll di• Scientist 1 – cell seeding

• Scientist 2 – reagent addition• Scientist 3 – compound spotting

• Scientist 1 – cell seeding• Scientist 2 – reagent addition• Scientist 3 – compound spotting

DEADLOCK!!DEADLOCK!!

Parameter changes in protocols difficult for users• FORMS!

Parameter changes in protocols difficult for users• FORMS!

Keeping environment and instruments contaminant-freeKeeping environment and instruments contaminant-free

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Other challenges

Offline use of instruments –vital to successOffline use of instruments –vital to successvital to success• Low intimidation factor

EL406 access

vital to success• Low intimidation factor

EL406 accessEL406 access• Potential solution: Turntable

EL406 access• Potential solution: Turntable

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Other challenges

Space limitationsZ t i t (DDR h)

Space limitationsZ t i t (DDR h)• Z-constraint (DDR reach)• Z-constraint (DDR reach)

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Advantage of phase approach

Phase Approach – Instead of one massive project with multiple moving parts and instrumentation we decided on a phasedPhase Approach – Instead of one massive project with multiple moving parts and instrumentation we decided on a phasedmoving parts and instrumentation, we decided on a phased project (Phase I, II, III)

• Room for scope changes

moving parts and instrumentation, we decided on a phased project (Phase I, II, III)

• Room for scope changes

• Changes in instrumentation needs (new instruments needed or current ones unnecessary)

• Change in ideas/process based on initial usage of system can be

• Changes in instrumentation needs (new instruments needed or current ones unnecessary)

• Change in ideas/process based on initial usage of system can be• Change in ideas/process based on initial usage of system can be reflected in future phases

• Change in throughput needs

• Change in ideas/process based on initial usage of system can be reflected in future phases

• Change in throughput needs

• Change in design• Change in design

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OCAP Time savings

Assay 1 (Proliferation Assay) – 384 well platesAssay 1 (Proliferation Assay) – 384 well plates

Manual (min) Automation (min)

Cell Seeding (20 plates) 90 20 (+10 min hands-on time)

Drugging (20 plates) 180+ 80 (+10 min hands-on time)

Reagent addition and read(20 plates)

100 60 (+5 min hands-on time)

Real life time savings example:• Veronica ran an assay that took 3 hours a day X 4 days a week = 12 hours

Real life time savings example:• Veronica ran an assay that took 3 hours a day X 4 days a week = 12 hours• Veronica ran an assay that took 3 hours a day X 4 days a week = 12 hours• With OCAP, her hands-on time is ~2.5 hours• Veronica ran an assay that took 3 hours a day X 4 days a week = 12 hours• With OCAP, her hands-on time is ~2.5 hours

Si ifi t ti iSignificant time savings

Support Reach

Currently, we support 16 labheads and ~25 associates for: • Small molecule drug discovery projects

Currently, we support 16 labheads and ~25 associates for: • Small molecule drug discovery projectsSmall molecule drug discovery projects• RNAi Screens• Combination screens

Small molecule drug discovery projects• RNAi Screens• Combination screens Projected to • Biologics projects

OCAP system1

• Biologics projects

OCAP system1

have ~25regular OCAP users by June • 1 superuser

• 2 regular users/trainers from our lab• 9 regular users from other labs across oncology

• 1 superuser• 2 regular users/trainers from our lab• 9 regular users from other labs across oncology

use s by Ju e2012

• In addition, many occasional users • In addition, many occasional users

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Assay Types/Readouts

Routine Assays Run within Oncology Format Comment

Reporter Gene Assays 384Assays

Cellular Surefire 384

Translocation HCI 384

N clear Co nt HCI 384 I D l tNuclear Count HCI 384 In Development

Proliferation 384

Proliferation combinations and

triples384

triplesAGP/HSA Shift

assays 384

Caspase Activation 384

Quantification ofQuantification of metabolites 384

Medulloblastoma -neurosphere assay 384 In Development

Transient Transfection Dual 96

Luciferase

MSD Assays - prep 96 In Automation Optimization

Roadmap






Approach



Approachpp

OCAP system details


pp

OCAP system details


Challenges

Assays

Challenges

Assays


Outlook


Outlook


37

Potential improvements

A single channel or 8 channel option on the BravoA single channel or 8 channel option on the Bravo

Continual optimization to decrease deadlocks

Turntables to allow access to instruments

Continual optimization to decrease deadlocks

Turntables to allow access to instruments

Greater z-reach for DDRs

Better docking tables

Greater z-reach for DDRs

Better docking tablesBetter docking tablesBetter docking tables

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OCAP outlook

Benchtop integrated workstationsBenchtop integrated workstations• Relieve OCAP as use increases• Single task focus

- Cell seeding only

• Relieve OCAP as use increases• Single task focus

- Cell seeding only- Plate reading only

Phase III will be determined by the logistics of use over the next 6 months and where we see need to increase

- Plate reading only

Phase III will be determined by the logistics of use over the next 6 months and where we see need to increasethe next 6 months and where we see need to increase throughput, ease, bottlenecks the next 6 months and where we see need to increase throughput, ease, bottlenecks

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Our Lab’s future vision

Fully functional, walk-away Biocel systemFully functional, walk-away Biocel system

Cell seeding and reading stations throughout lab space

Specialized readers (ie HCI Biacore MSD) become

Cell seeding and reading stations throughout lab space

Specialized readers (ie HCI Biacore MSD) becomeSpecialized readers (ie HCI, Biacore, MSD) become modular and/or stand alone with stackers/mini-arms while off system

Specialized readers (ie HCI, Biacore, MSD) become modular and/or stand alone with stackers/mini-arms while off system

1-2 power users with broad programming capabilities

Growing users that can train one another

1-2 power users with broad programming capabilities

Growing users that can train one anotherGrowing users that can train one another

Full Schedule both day and night

Growing users that can train one another

Full Schedule both day and night

More time to interact with data sets More time to interact with data sets 40

Suggestions, based on our experiences...Part I

New projects and users should give adequate notice then set appropriate expectations as to when their solutions can be put in place and full use of New projects and users should give adequate notice then set appropriate expectations as to when their solutions can be put in place and full use of p p presources can commence

Have a good interactive computer-based scheduling system

p p presources can commence

Have a good interactive computer-based scheduling system

Strongly encourage all associates to be trained on Instruments and Equipment as an opportunity for future successes and streamlining

Ensure that you understand the scope and timelines of projects

Strongly encourage all associates to be trained on Instruments and Equipment as an opportunity for future successes and streamlining

Ensure that you understand the scope and timelines of projects

Standardize as much as possible – be creative – think out of the box

Be courteous, supportive (even on your worst day) – no fear or question h ld dd d

Standardize as much as possible – be creative – think out of the box

Be courteous, supportive (even on your worst day) – no fear or question h ld dd dshould go unaddressed

Decide together on Data solutions

should go unaddressed

Decide together on Data solutions

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Suggestions, based on our experiences...Part II

Have a list of all contacts involved in the Project in order to provide sufficient communicationHave a list of all contacts involved in the Project in order to provide sufficient communicationcommunication

Stay in the project loop as appropriate – meet as frequently as necessary to get them onboard

communication

Stay in the project loop as appropriate – meet as frequently as necessary to get them onboard

Acquire a patient, flexible staff with excellent communication skills

Partner with each and every lab utilizing the facility

Acquire a patient, flexible staff with excellent communication skills

Partner with each and every lab utilizing the facility

Superuser - preferably an engineer, Assay Development specialist in DA specific areaSuperuser - preferably an engineer, Assay Development specialist in DA specific area

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Agilent Technologies• Jeff HsuAgilent Technologies• Jeff Hsu

Waste hole phenomenon• Jeff Hsu• Marty Thomae• Pete Werner

• Jeff Hsu• Marty Thomae• Pete Werner• Brian O’Sullivan• Robert Vandenburg• Steve Ciaccio

• Brian O’Sullivan• Robert Vandenburg• Steve Ciaccio• OCAP project team

Novartis

• OCAP project team

Novartis• Chris Igo• Ted Manley• Brian Duffy

• Chris Igo• Ted Manley• Brian DuffyBrian Duffy• Cellular Assays Team

Brian Duffy• Cellular Assays Team

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An Interactive Automation Experience – Oncology … · An Interactive Automation Experience ......

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