Whole Genome Sequencing (WGS) workflows demand robust automation that balances throughput, reproducibility, and traceability. For high-throughput sequencing labs, the ability to process hundreds of DNA samples per day with minimal operator touchpoints is essential to meet demand at scale.
At HighRes Biosolutions, we design modular automation systems capable of processing thousands of DNA samples in under 24 hours. This write-up explores a representative architecture for a WGS production system, designed around pre- and post-PCR workflows, and optimized through CellarioScheduler simulations to automate library preparation from 384 DNA samples across four 96 well plates per day.
Workflow Goals: End-to-End DNA Processing at Scale
This representative WGS system was designed to deliver:
- DNA QC and Normalization across hundreds of samples per run
- Automated library preparation including fragmentation, bead cleanup, adaptor ligation, and size selection
- Parallelized PCR enrichment and purification
- Post-PCR QC and pooling for sequencing-ready libraries
The operational target was to process 384 samples daily while ensuring assay consistency, minimized consumable waste, and compatibility with stringent sequencing QC requirements.
Figure 1. Representative system for WGS production.
System Architecture: Modular, Pre/Post-PCR Design
The system layout reflects the need to separate Pre-PCR and Post-PCR environments, while maintaining fully automated sample handoffs.
Figure 2. Design layout of representative WGS production system.
Pre-PCR devices include:
- Liquid Handling: 2x Beckman Coulter Biomek i5 (Span-8)
- Robotics & Storage: HighRes ACell robotic arm on rail, PlateHotels, Cytomat incubators (ambient + refrigerated)
- Consumables & Prep: Plate sealer (Agilent PlateLoc), plate peeler (Azenta Automated Plate Seal Remover (formerly Brooks XPeel®), barcode scanner, LidValet, and PlateOrient
- Reagent Handling & Mixing: Multidrop Combi dispenser, BioShake mixers, MicroSpin centrifuge, magnetic base nests
- Expansion Capacity: Space for Covaris LE220R fragmentation and additional modules
Post-PCR devices include:
- Liquid Handling: Beckman Coulter Biomek i5 (Span-8)
- Robotics & Storage: HighRes ACell robotic arm on rail, PlateHotels, Cytomat incubator, automated airlock doors
- Amplification & QC: QuantStudio qPCR, Agilent Fragment Analyzer, Varioskan LUX multimode reader
- Consumables & Prep: PlateLoc/Automated Plate Seal Remover (formerly XPeel®), barcode scanner, LidValet, PlateOrient
- Reagent Handling & Mixing: Multidrop Combi dispensers, MicroSpin centrifuge, magnetic base nests
This modular approach ensures that scale-up is straightforward due to additional hotels or secondary liquid handlers that can be integrated without redesigning the full system.
Workflow Considerations: Protocol Design in 9 Parts
Cellario protocols were designed and simulated in nine linked parts, each reflecting a stage of the sequencing prep workflow.
Figure 3. CellarioScheduler Protocol Overview for Part 3: Fragmentation
- DNA QC – stamping to fragment analysis plates (~3 hours)
- DNA Normalization & Cherry Pick – compression from multiple input plates (~2.5–4 hours)
- Fragmentation – manual Covaris fragmentation step, with automated handoff back to the system (~2 hours with operator interaction)
- Bead Cleanup, End Repair, Adaptor Ligation, Size Selection – fully automated on-deck workflow (~5–7 hours)
- PCR Enrichment – 3–4 thermal cyclers running in parallel (~1.25 hours)
- Post-PCR Cleanup & Quantification (~3.5 hours)
- Library Cherry Pick & Normalization (~1.5 hours)
- Library QC with fragment analysis and quantification (~3 hours)
- Pooling – final prep for sequencing (~20 minutes)
Simulations confirmed that the complete set of protocols could process 4 plates (≈384 samples) in ~22–23 hours.
Smart Scheduling with CellarioScheduler
A key enabler of this throughput is CellarioScheduler, which allows the workflow to run as an integrated, parallelized process.
- Parallelization – DNA QC, bead cleanup, and QC devices operate across multiple plates simultaneously.
- Bottleneck Management – Scheduler staggers handoffs between fragment analysis and PCR, avoiding idle time
- Real-Time Visualization – Operators can view Gantt charts showing device usage and completion predictions
- Scalability – Adding additional Biomek i5/i7 workstations can further reduce cycle times without rewriting protocols
Figure 4. Gantt chart showing real-time visualization of device usage and completion predictions.
Software Integration: Future-Ready with CellarioOS
The system is designed to integrate seamlessly into CellarioOS, providing:
- Ability to publish protocols flexibility and simplified ordering
- Full traceability across the entire library preparation process
- Access to utilization data
- LIMS integration for downstream sequencing and reporting
What This Example Shows
This representative WGS production system demonstrates how HighRes designs scalable, modular sequencing workflows that balance throughput, reproducibility, and flexibility. By anchoring the workflow on Biomek i5 workstations, integrating robust pre- and post-PCR automation, and leveraging CellarioScheduler for intelligent scheduling, the system achieves high daily throughput with minimal operator intervention.
At HighRes, we co-design production-ready workflows that evolve with scientific demand.
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