DEDICATED - PerkinElmer€¦ · 1 2 3 Liquid Transfer. Cellular Applications. 6 Customer Request...
Transcript of DEDICATED - PerkinElmer€¦ · 1 2 3 Liquid Transfer. Cellular Applications. 6 Customer Request...
cell::explorer™
cell::explorer gene pro and HTS pro
DEDICATEDROBOTIC APPLICATIONWORKSTATIONS
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Turn questions into breakthroughs
At PerkinElmer, we share your
commitment to answering challenging
biological questions. Our broad portfolio
of instruments, reagents, software
and laboratory services empower you
to do more.
With the cell::explorer workstations,
we combine these individual portfolio
elements into dedicated integrated
automated workstations. From cellular
screening and cellular imaging applications
to high-throughput screening, genomics
and DNA/RNA-based applications, we
provide a focused workstation concept
to enable you to focus on the application
rather than robots.
FULLY INTEGRATED ROBOTIC AUTOMATION DEDICATED TO YOURBIOLOGICAL APPLICATION
Table of Contentscell::explorer- Cellular Applications ................................... 3
Stem Cell Cultivation and Phenotypic Screening ............................. 3
Cell Culture and Viral Amplification Workstation ............................ 6
Gene Expression Analysis and High Content Screening .................. 8
Secondary HCS Workstation .......................................................... 10
cell::explorer gene pro—Genomic Applications .............. 12
Fully Integrated Automated Genotyping ....................................... 12
RNA-based High-throughput Expression Analysis Workstation .... 14
Cell Line Screening and Cherry Picking .......................................... 16
High-throughput, High content RNAi Screening ............................ 19
cell::explorer HTS Pro—High-throughput Screening ....... 21
High-throughput 1536 Well Plate Target Discovery ..........................21
Multimodule High-throughput Screening Platform ...........................23
High-throughput AlphaLISA® ELISA Alternative Screening ...............25
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Stem Cell Cultivation and Phenotypic Screening
Customer Request
Two independent workstations for stem cell cultivation and screening of phenotypic assays.
Configuration Requirements
• Two independent workstations
• Cell cultivation, media exchange and stem cell differentiation
• Able to run multiple experiments in parallel, up to 4 x 220-plate batches
• Stem cell phenotypic compound screening
• High throughput hardware and software
• Automated lid-handling, plate sealing and unsealing
• Flexible scheduling software allows for multiple batches of experiments to be run in parallel with the ability to add batches, as needed
• Compact design
• HEPA filtration to prevent contamination
• Automated plate transfer between two workstations allows for complete integrated solution
Figure 1. cell::explorer™ Stem Cell Cultivation workstation.
Accurate high throughput stem cell phenotypic screening provides researchers valuable insight on how complex compound matrices effect cell culture or the differentiation process. Automation of both the upstream cell culture and subsequent assays increases efficiency and greatly enhances compound screening.
The two cell::explorer™ workstations are designed to work in parallel, one for cell culture and differentiation and the other for downstream screening. Both systems are posi-tioned within a single HEPA filtration enclosure to prevent sample contamination. The cell culture workstation with job::manager scheduling software is designed to run up to four 220-plate batches in parallel; providing control and calendar-like graphical management.
After cell cultivation and differentiation process in the first workstation, the plates are transferred to the second system for phenotypic screening.
Cellular Applications
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Stem Cell Culture and Differentiation Configuration
Figure 2. Stem Cell Culture workstation (enclosure not shown).
plate::handler6 axis robotic arm
C24 Incubator
shaker
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JANUS Mini MDTLiquid Handling
JANUS Mini MDTLiquid Handling
Lid Handler
plate::liftPlate storage Turntable
Plate distribution6
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ELX 406Washer dispenser
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PerkinElmer Components 3rd Party Components
Stem Cell Culture and Differentiation ProcessOne of the independent workstations is designed to maintain and monitor stem cell cultures prior and during the differentiation process. Multiple experiments (up to 4 x 220-plates) can be managed via job::manager software.
job::manager Software Process Planning and Remote Control SoftwareThe software enables complex scheduling of multiple processes and remote access to ensure optimal efficiency during long cell culture differentiation protocols. This becomes essential when long experiments can be split into more smaller processes (e.g. long cell differentiation or maintenance automated processes). Using the “variable change function,” a previous process could change parameters of a following process automatically; thus, allowing for a flexible and adaptable system. Figure 3. job::manager software calendar view.
Cellular Applications
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Phenotypic Stem Cell Screening Configuration
PerkinElmer Components 3rd Party Components
Figure 4. Phenotypic Stem Cell Screening workstation (enclosure not shown).
plate::handler6 axis robotic arm
C24 Incubator
Roche Peeler
Reader
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JANUS Mini MDTLiquid Handling
JANUS Mini MDTLiquid Handling
Lid Handler
plate::liftPlate storage
TurntablePlate distribution
6shaker
C6001 Incubator
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ELX 406Washer dispenser
Stem Cell compound Screening Process
Incubation
Read-out
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Liquid Transfer
Cellular Applications
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Customer Request
Dedicated workstation for cell culture, cell viability control and viral protein amplification.
Configuration Requirements
• Highly flexible cellular workstation with:
– AutoFlask™ cell culture and 24- and 96-well plate formats
– Separate AutoFlask™ high volume media filling unit
– Fully enclosed operator and product safety enclosure
– Cell viability and plate reading capabilities
– Separate sealer, cell dispenser and shaker
• Control software for long-term culturing processes with automatic control of cell culture time through cell counter feedback.
This workstation was designed to enable the production of a large set and number of target proteins. Using a virus vector system to infect cells and produce the target proteins, the cell::explorer™ high content screening platform is able to provide cell cultivation, transfection, viability and GFP expression detection in a single platform. As most cell culture processes are lengthy, job::manager provides an enhanced level of support by monitoring and controlling several
individual plate::works™ processes, simultaneously. With job::manager, you can divide longer processes into shorter ones, and leverage the ‘idle time’ for another (independent) process to run. And, with its variable change function, you can update or append proceeding tasks remotely.
Figure 5. 3D view of cell culture and viral amplification system*
* Enclosure not shown to highlight internal components.
Cellular Applications
Cell Culture and Viral Amplification Workstation
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Example Workflow
Transfection
Viral Production
Small-scale Protein Production
JANUS® Automated Workstation
Expanded Deck with VariSpan® and MDT
AutoFlask™ Filling UnitMedia dispenser
EnVision®
Multilabel plate reader
MultiDrop® CombiReagent dispenser
Incubators and Hotel
plate::shuttle On deck plate move-ment and AutoFlask™
filling position
plate::handler™
6 axis robotic armLid handler and barcode reader
PlateLoc Plate sealer
Guava EasyCyte™ Cell counter
PerkinElmer Components
3rd Party Components
Figure 6. Top view of cell culture workstation without enclosure.
Figure 7. Dispense large volumes of 8 different media into AutoFlasks™ with VariSpan arm and easily moveto AutoFlask™ for filling.
Figure 8. Screenshot of job::manager interface; easily manage multiple plate::works processes for maximum productivity.
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Cellular Applications
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Gene Expression Analysis and High Content Screening (HCS)
Customer Request
Flexible robotic workstation to support real-time PCR, multiplexing and high content screening (HCS) for an academic research facility.
Configuration Requirements
• Highly flexible assay platform
• Supports 96- and 384-well plate formats
• HEPA filtration for cell preparation
• Ability to conduct parallel processing and independent, parallel use of the workstation modules
• Supports multiple application techniques including:
– Automated real-time PCR
– Multiplex assays
– HCS with cell-based readouts
– nl compound transfer and cherry picking
Today’s academic researcher requires a flexible screening platform to support multiple microplate formats, liquid volume transfer and different read-out methods. For novel systems biology, cancer research and pathway analysis, a platform that supports multiple detection methods and complete automation enables researchers to generate better data results and make more confident decisions.
This robotic workstation platform was designed to accommodate both gene expression analysis and perform HCS for molecular medicine research. Equipped to perform real-time PCR techniques as well as multiplexing, the platform included key components to support both research areas and address the customer’s flexibility requirements.
Figure 9. 3D view of a gene expression analysis and HCS platform.
Cellular Applications
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Lid Handling UnitLid removal, storage and replacement dispenser
HEPA FilterSterile air filtration
Seal peelerPeels seals
FLEXMAP 3D® Multiplex Platform
MultiDrop® CombiReagent dispensing
LightCycler® 480Real time PCR
SealerSeal plate
Echo®
Low volume liquid transfer
Operetta®
Confocal microplate imaging reader
JANUS® Automated Workstation For plate transport between devices
EnVision™
Multilabel Plate Reader
plate::handler™ 6-axis robotPlate transfer
Barcode ReaderRead Barcode
TurntablePlate transfer
ELX 405 WasherLiquid handling
workstation (4 tip)
PerkinElmer Components
3rd Party Components
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plate::lift – get new plate plate::lift – get new plate
BC reader – read barcode BC reader – read barcode
JANUS – transfer
JANUS – mix 4 times
Sealer – seal plate
LightCycler – 95° C 2 min
Incubator – 40° C 2h
Incubator – 10 min 40 °C w/o lid
Peeler – peel seal
MultiDrop – add reagent
JANUS – tip mix
JANUS – add reagent
JANUS – tip mix
FLEXMAP 3D – read out
Assay plates Source plates
Example Workflow Process
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Figure 10. Top view of the gene expression platform configuration; component labels identify the instruments relevant to the example workflow shown below.
Cellular Applications
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Cellular Applications
Secondary High Content Screening Workstation
Customer Request
Fully automated high-throughput cellular screen ing platform to support both, high content and conventional multimode readouts.
Configuration Requirements
• Support for 96- and 384-well plates
• Integrated high content screening (HCS) and multimode reader
• Flexible liquid handling, supporting use of single-use pipette tips
• Solutions for plate shaking and centrifugation
• Throughput in line with reader capabilities (i.e. robotics and liquid handling must not be throughput limiting)
• Advanced error handling
• 24-hour operations
• HEPA filtration hood for product protection
• Option to use devices offline
Cellular assays and especially those utilizing high content readout and analysis techniques offer numerous advantages over biochemical screening methods. High-throughput imaging readers like our Opera®, in conjunction with dedicated automation and liquid handling components enables researchers to deploy high content screening techniques at much earlier stages of the drug discovery process than previously possible.
For an academic customer we built a flexible cellular screening workstation to support both, high content and regular cellular assays via an integrated Opera and EnVision® reader. Inside the compact cell::explorer™ housing a variety of liquid handling components including a centrifuge and a shaker were grouped around an 6-axis robotic arm. To increase throughput and to feed the Opera with ready-to-screen plates while simultaneously carrying out a different screening run the Opera was connected to a four position turntable with adjacent 300+ capacity plate storage unit.
This integrated turnkey system was able to prepare and read 40 assay plates in less than 8 hours including, the preparation of an aqueous dilution plate.
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Cellular Applications
OperaConfocal microplate imaging
TurntableFast parallel plate transport and buffering
plate::liftAmbient labware
storage (300+ plates)
Lid Handling Unit and Barcode Reader Lid removal, storage and replacement
Thermo Multidrop CombiBulk reagent addition
Liconic STX220 IncubatorTemperature and CO2 controlled incubation
BioTek ELx405Plate washing
EnVisionMultimode plus reading
plate::stacker 15-position random access
plate storage
Barcode Reader Barcode reading
(compound plates)
plate::handler 6-axis robotPlate transport between devices
FlexDrop4 channel reagent dispensing
PlateStakTip box storage
Thermo Teleshake 384Plate shaking
JANUS Mini MDTLiquid handling
Velocity11 VSpin Centrifuge
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JANUS transfer CP to IP add
controls
JANUS transfer IP to AP
incubator
Assay Plates (AP) Intermediate Plates (IP) Compound Plates (CP)
Example Assay Flow
plate::liftplate::lift
plate::lift
centrifuge
plate::lift
teleshake
Multidrop
incubator
PlateStak
FlexDrop
Opera
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Figure 11. Top view.
HEPA Filter UnitProduct protection
cell::explorer EnclosureA full enclosure for robotic safety, product and dust protection
Figure 12. 3D view.
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PerkinElmer Components
3rd Party Components
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Genomic Applications
Fully Integrated Automated Genotyping
Customer Request
Workstation automating genetic characterization of mice strains used in antibody production.
Configuration Requirements
• Walk-away automation for DNA extraction, DNA normalization, PCR plate preparation and real time PCR with fully integrated data tracking and report generation
• Two integrated JANUS® automated workstations for high throughout, parallelized liquid handling
• Highly efficient, automated DNA extraction utilizing proven PerkinElmer chemagic bead based nucleic acid extraction technology
• Fully automated DNA normalization based on readout from dye free, LabChip® DS microliter microplate reader
• 2x integrated Roche LightCycler® 480 real time cyclers for parallel qPCR processing
• Flexible scheduling software
Genetic characterizing of animals used in research and production of therapeutic antibodies can be an arduous, time-consuming step. The system we have designed provides walk-away automation for all genotyping processes starting with DNA extraction, DNA normalization, PCR plate preparation and real time PCR in a compact, space-saving format.
With our automated system, DNA extraction from up to 8 x 96 mice tail or ear clippings, the full genotyping workflow with DNA normalization, PCR plate preparation and real time cycling can be completed within a single working day creating a concise report linking initial 2D sample IDs to qPCR results.
Figure 13. cell::explorer gene pro™ (enclosure not shown).
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Genomic Applications
JANUS Mini VariSpan™Liquid Handling with PlateStak® for tip box supply
JANUS StandardVariSpanLiquid Handling
chemagic 360DNA extraction
plate::handler6 axis robotic arm
Hotel220 plate storage
2D Barcode ScannerFlat bed
PlateLocksealer
Centrifuge
RocheLightCycler® 480Real time PCR
Barcode Labeler
LabChip DS
Figure 14. Genotyping workstation (enclosure not shown).
General workflow:
The workflow on the right side describes, very generically, the genotyping process - DNA extraction, normalization and DNA amplification.
DNA extraction
[DNA] measurement
DNA normalization
PCR plate preparation
Real time PCR
PerkinElmer Components 3rd Party Components
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Genomic Applications
RNA-based High-throughput Expression Analysis Workstation
Customer Request
cell::explorer™ gene pro workstation for automated high throughput RNA expression analysis based on real time PCR.
Configuration Requirements
• Workstation with high throughput expression analysis capacity performing greater than 1,000 expression analysis steps per hour
• Up to 4x real time PCR cyclers
• Full walk-away capabilities for 24/7 operation
• HEPA filtration capability to prevent contamination
Using RNA in drug discovery has increased the need for high throughput technologies.
We designed the cell::explorer gene pro workstation specifically for this application with a HEPA filtration enclosure to prevent contamination. To meet the high throughput demands, the system is designed to automate the entire process, from plate preparation, incubations, plate sealing and real time PCR processing steps. The cell::explorer gene pro is able to achieve 20,000 real time PCR preparations and PCR reactions in 24 hours.
Figure 15. cell::explorer gene pro for expression analysis.
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Genomic Applications
RNA-based High Throughput Expression Analysis
Figure 16. cell::explorer gene pro workstation (enclosure not shown).
plate::handler6 axis robotic arm
Freezer
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JANUS MDT and VariSpanLiquid Handling
EnSpirePlate reader
Sealer
PlateStakPlate storage Turntable
Plate distribution
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Real time PCR2 x 2 units stacked
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centrifuge
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DispenserPlate hotel
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RNA expression analysis process
RNA sample plate
Add master mix
Spin down plate
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Real time PCR5
Transfer sample into PCR plate
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Genomic Applications
Cell Line Screening and Cherry Picking
Customer Request
Two integrated workstations for screening and subsequent picking of antibody-producing hybridoma cells.
Configuration Requirements
• LIMS system to control all functions of each module/ workstation with data exchange capabilities via XML files
• Automation supporting high-throughput screening (>750 x 96 plates in 24 hours)
• Automation to support cherry picking (>14,500 picks in 24 hours)
• Liquid handling to accommodate cherry picking, optional assay plate preparation and exchange of cell culture medium
• ‘Class 100’ clean room environment
• 24/7 performance for complete ‘walk away’ automation
To maximize resources and increase productivity, biotechnology organizations often require their instruments to perform with a 24/7 operations capacity. In this example, PerkinElmer developed a workstation platform that could support both cell line screening and cherry picking application techniques in a standardized operating environment.
To address the throughput requirements of cell line screening, the cell::explorer™ gene pro workstation configuration included
a unique turn table concept which allows multiple micro-plates to be handled in parallel. The microplates are first exported from a 196-plate hotel and initially transported (by coordinated pull/push movements and turn table rotation) to two (2) multidrop dispensers, and then on to a 44-posi tion microplate hotel for incubation. The prepared microplates are then loaded into a microplate reader where the samples are read, and the date read-outs are produced.
For high-throughput cherry picking applications it is essential to reduce plate exchange times to a minimum. With the module designed for this application, the required reductions in plate exchange time was achieved by integrating a turntable in front of the incubator. With four (4) plate buffer positions, a turntable can receive a picked plate and immediately provide a new “to be picked” plate. Thereby, reducing the time con suming import and export steps which can be further delayed when the liquid handling instrument is occupied with performing the ‘picking’. To transport the microplates from the turntable to the liquid handling instrument, we integrated a 6-axis industrial robot , which also served as the means for loading the microplates into the inte grated barcode labeler. Moreover, each workstation module was outfitted with a 3x HEPA filter to create and ensure a ‘Class 100’ clean room environment.
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Genomic Applications
EnVision™Multilabel Plate Reader
TurntableParallel plate distribution
MultiDrop® Combi Reagent dispenser
MultiDrop® Combi Reagent dispenser
Liconic LPX44 Plate HotelIntermediate ambient temperature incubation
Liconic LPX220 Plate HotelAssay plate storage
PerkinElmer Components
3rd Party Components
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Figure 17. Top view of screening workstation with labels to illustrate each component’s process.
Class 100 enclosureVery low particle amount in the air
Figure 18. 3D view of a screening workstation with a Class 100 enclosure.
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Example process
96-well plates
Microplates in plate hotel
MultiDrop1 add reagent
Add 2nd reagent
Incubate
Read
Return to microplate hotel
Screening Workstation
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JANUS® Automated WorkstationEquipped with VariSpan and MDT Arms for cherry picking and medium exchange
PlateStak® (2x)Tip box storage and transfer to JANUS
plate::handler™ 6-axis robotplate transport between devices
Lid handling unitLid removal, storage and replacement
MultiDrop® CombiReagent dispensing
BarCode LabelerPrints and apply barcodes to plates
Liconic STX 500 IC Assay plate storage
TurntableFast parallel plate distribution
Genomic Applications
PerkinElmer Components
3rd Party Components
Figure 19. Top view of cherry picking workstation with labels to illustrate each component’s process.
Class 100 enclosureVery low particle amount in the air
Figure 20. 3D view of a cherry picking workstation with a Class 100 enclosure.
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Cell plates Cherry Picking Process
Receiving plates
Incubator
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Lidding
Add reagent
Incubator
Incubator
JANUS automated cherry picking
Incubator
Barcode labeler
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Genomic Applications
High-throughput, High Content RNAi Screening
Customer Request
Fully automated platform for high content small interfering RNAs (siRNA) and general compound screening.
Configuration Requirements
• Small footprint
• Fully integrated system
• Capacity to process 260+ plates in a single run
• Flexible liquid handling supported by single use pipette tips
• Throughput in line with reader capabilities (robotics and liquid handling must not limit throughput)
• Long term (i.e. 48 hr.) incubation capabilities with access to HCS reader offline during incubation periods
RNA interference is a specific, potent, and highly successful approach for studying mammalian gene function. More-over, high-throughput screening of small interfering RNAs (siRNA) libraries has quickly become an important tool for drug discovery and biomedical research. RNAi screening becomes even more powerful when combined with high content imaging and data analysis techniques as the resulting multiparametric readouts provide greater insight toward the understanding of gene function.
For an academic customer, we built a fully integrated RNAi screening system to be deployed in a space restricted environment. Inside the compact cell::explorer™ gene pro enclosure a BioTek® EL406 microplate washer/dispenser, JANUS® Mini MDT liquid handling platform with 384-well pipetting head and 2 PlateStak® units with supply tip boxes were configured around a 6-axis robotic arm. Cell and bulk reagent dispensing is handled by a Thermo® Multidrop Combi dispenser unit. To support their high content plate reading, an Opera® high throughput imaging reader was integrated via a 4-position turntable adjacent to a 300+ capacity plate storage unit (plate::lift). The turntable and plate::lift provides the Opera with ready to read plates (prepared off-line) while the remainder of the system is engaged in liquid handling and/or plate incubation.
With respect to storage and incubation capacity, the application-specific configuration was designed to facilitate screening of a 100,000 well compound library within a single run.
Figure 21. cell::explorer gene pro for RNAi screening.
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Genomic Applications
OperaConfocal microplate imaging
TurntableFast parallel plate transport and buffering
plate::liftAmbient labware storage (300+ plates)
Barcode reader Barcode reading (assay plates)
Lid handling unit Lid removal, storage and replacement
plate::handler 6-axis robotPlate transport between devices
BioTek EL406 Plate washing and reagent dispensing
Thermo Multidrop Combi Cell and bulk reagent dispensing
Liconic STX 110 incubatorTemp. & CO2 controlled incubation
plate::stacker 30 Position random access plate storage
Barcode reader Barcode reading (cmpd, siRNA plates)
PlateStak (2x) Tip box storage (48x)
JANUS Mini MDTLiquid handling
PerkinElmer Components
3rd Party Components
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Figure 22. Top view.
cell::explorer enclosureA full enclosure for dust protection and robotic safety
Figure 23. 3D view.
Cell PlatesForward Transfection Process
Reverse Transfection Process
RNAi Plates
RNAi Plates
incubator
incubate 48 hr.plate::lift
add ligand
read
read
incubator / waste
incubator / waste
plate::lift
add transfection reagent
incubate 15 min.
add cells
incubate 48 hr.
add ligand
incubate 24 hr.
JANUS transfer RNAi to cell plates
plate::lift
add transfection reagent
incubate 15 min.
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High Throughput Screening
High-throughput 1536 Well Plate Target Discovery
Customer Request
HTS platform for versatile High Throughput Screening (HTS) processes.
Configuration Requirements
• Low volume dispensing and compound transfer for 1536 well plate applications
• Versatile system configuration for biochemical, cell-based and cell imaging applications
• Two smaller workstations operate in parallel to increase efficiency and reduce cross contamination between compound reformatting and assay screening aspects of the workflow
• High throughput industrial robot automation
• Enclosed system with HEPA filtration
Drug Discovery workflows require tools and technologies that can support a broad range of current and future applications including multiple microplate formats, liquid transfer volumes and detection-based read-out methods. The cell::explorer HTS pro platform was designed to fulfill those diverse needs. Here we describe a configuration that was developed to accommodate two independent process work-station modules linked with a turntable mechanism to produce a fully capable integrated screening system designed to automate the entire screening process. With an integrated 2 x 500 plate storage capacity, the compound workstation module has access to 384,000 compounds in 384-well plate format. Precision dispensing was critical for all aspects of the workflow. Compounds are aliquoted (nL amounts) into the assay plate using a Labcyte ECHO acoustic dispenser, while reagent and cells are transferred with Gyger Certus (nL dispensing) and Termo MultiDrop® Combi (µL dispensing) instruments. Assay results are detected either on a EnVision® Multilabel Plate Reader or on an Opera® Phenix confocal microplate imaging reader.
Figure 24. cell::explorer HTS pro dual workstation configuration.
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High Throughput Screening
Configuration
Figure 25. cell::explorer HTS pro dual workstation configuration – top view.
Centrifuge and Sealer
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Opera PhenixImaging Reader
TurntablePlate Shuttle
EnVisionMultiMode Reader
JANUS StandardLiquid Handling with PlateStak for Tip Box Supply
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plate::handler6 Axis Robotic Arm
2D Barcode ScannerFlat Bed
XpeelPlate Peeler
Washer/ Dispenser
Nanoliter Dispenser
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Incubator220 Plate Incubation
{ {Cell::explorer HTS pro dual workstation (enclosure not shown)
Assay Plate Preparation Workstation Module Compound Plate Preparation Workstation Module
General WorkflowThe generic HTS process workflow is described here. Compound plates are prepared on the workstation located on the right and assay plates on the left side workstation.
General HTS Screening Process
Compound Transfer
Incubation
Readout
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PerkinElmer Components 3rd Party Components
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High Throughput Screening
Multimodule Ultra- High Throughput Screening Platform
Customer Request
A multimodule system that can accommodate both uHTS and HCS in one, integrated platform.
Configuration Requirements
• Fully integrated screening platform to support:
– 96, 384, 384 low volume and 1536-well plates
– nL to high μL liquid handling
– Detection instruments for HCS – image based readouts
– Cellular and biochemical multimode readouts
• Parallel assay processing and offline use of individual instruments
• Parallel and offline access to both workstation modules
Today’s academic researchers require tools and technologies that can support a broad range of current and future appli cations including different microplate formats, liquid handling volumes and detection-based read-out methods; cell::explorer HTS pro was designed to fulfill those diverse needs. The configuration was created with four (4) individual workstations, each able to run independent processes, linked via a bi-directional con veyor belt to create a large integrated screening system poised to automate the entire screening process. Through two (2) integrated 500-plate capacity stores, the compound module has access to nearly 600,000 compounds stored in 384-well plates. Compounds can be transferred into assay plates either in nL amounts utilizing a Labcyte ECHO acoustic dispenser or in μL amounts through a JANUS® Automated Workstation fitted with both 96- and 384-well pipetting heads. Precision dispensing of reagent and cells is realized through a Flexdrop® IV and two Thermo MultiDrop® Combi dispensers spread over the indi vidual modules. A 198-plate incubator, as well as 40-plate incubator enable plate incubation at different environmental condi tions. Assay results are detected either on an EnVision® Multilabel Plate Reader or on an Opera® confocal microplate imaging reader.
Figure 26. 3D view of multimodule uHTS platform.
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High Throughput Screening
FlexDrop® IV High precision reagent & cell dispenser
Conveyor beltPlate distribution conveyor dispenser
Cytomat® 6001 IncubatorIncubation
Echo®
nl compound transfer
Washer
MultiDrop® CombiReagent dispenser
500 DC storeCompound plate storage
1000 DC storeCompound plate storage
MultiDrop® CombiReagent dispenser
EnVision®
Multilabel Plate Reader
plate::handler™ 6-axis robotPlate handling robot
plate::handler™ 6-axis robotPlate handling robot
TurntablePlate handling device
Opera®
Confocal microplate imaging reader
JANUS® Automated WorkstationMINI Varispan® with 4 tips
plate::handler™ 6-axis robotPlate handling robot
Lid handling unitLid removal, storage and
replacement
JANUS® Automated WorkstationMINI MDT for 96/384 tips
VSpin centrifugePlate centrifugation
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Figure 27. Top view of multimodule HTS and HCS platform.
Figure 28. View of system within a research facility.
Assay plates Compound plates
Example Assay Flow
Image plate
Compound store
Compound store
Incubator 1
Add reagent 1
Add reagent 2Read barcode
Incubator
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Wash plate
Wash
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High Throughput Screening
High-throughput AlphaLISA ELISA Alternative Screening
Customer Request
Fully automated platform for high-throughput AlphaLISA® screening.
Configuration Requirements
• Small footprint
• Fully integrated system
• Capacity for 20 Assay and 40 Sample plates is 8 hours, including tip change
• Ability to process plates in batches with each batch using a different protocol
• Flexible liquid handling supporting use of single-use pipette tips
PerkinElmer’s AlphaLISA technology is a novel, homogeneous, bead-based assay technology which can be used to replace traditional ELISA assays in drug discovery, diagnostics and basic research. Because AlphaLISA assays are homogeneous, they can easily be automated. As an added value, AlphaLISA technology has been demonstrated to successfully work in high density formats (384- and 1536-well plates) enabling researchers to run high numbers of samples in small sample volumes.
Utilizing our proven cell::explorer™ HTS pro platform, we have designed a true “all out of one hand” fully automated high-throughput AlphaLISA screening platform for use by a major pharmaceutical company. Sample transfer and standard addition are carried out by a PerkinElmer JANUS® automated liquid handling platform fitted with 96-tip pipetting head while antibody solution and AlphaScreen® beads are dispensed by 2x PerkinElmer FlexDrop® IV dispensers. The two FlexDrops provide a total of 8 independent dispense channels enabling the operator to run plates using different protocols within one run. Following incubation, plates are read on PerkinElmer’s EnVision® multimode reader.
Emission615 nm
Excitation680 nm
Streptavidin-coatedAlpha Donor Bead
Anti-insulin Acceptor Bead
BiotinylatedAnti-analyte
Analyte
Figure 29. AlphaLISA cell::explorer workstation.
Figure 30. Example AlphaLISA insulin assay.
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High Throughput Screening
plate::stacker Ambient plate storage/incubation
FlexDrop IV (2x) Reagent dispensing
Barcode reader Barcode reading
Lid handling unit Lid removal, storage and replacement
JANUS Mini MDTLiquid handling
Liconic LPX220 plate hotel
Plate and tip box storage
plate::handler 6-axis robotPlate transport between devices
EnVision AlphaScreen Reader
2
1
3 4
5
67
8
PerkinElmer Components
3rd Party Components
Multilabel and Multimode Detection Instruments
PerkinElmer offers several multimode detection instruments to support your AlphaLISA assays including
the EnVision® (top) and EnSight™ plate reader.
hotel
Tip Boxes Assay Plates (384-well)
Sample Plates (96-well)
Typical Assay Flow
hotel
hotel
delid plate
delid plate
delid plate
delid plate
lid plate
lid plate
lid plate
lid plate
hotelhotel
read barcode read barcode
incubate, 30 min.
read
FlexDrop• add donor beads
incubate, 60 min.
waste
JANUS • load new tips• transfer samples
(in duplicates) to assay plate
• unload tips
FlexDrop• add acceptor beads• add biotinylated Ab
2 2 2
2
2
7 7
1
4
4
5
5
8
Figure 31. Top view.
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Copyright ©2015, PerkinElmer, Inc. All rights reserved. PerkinElmer® is a registered trademark of PerkinElmer, Inc. All other trademarks are the property of their respective owners. 012473_01 PKI
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For Research Only. Not for use in diagnostic procedures.