Automating Cell-Based Assay Development: A Representative System

Cell-based assays are foundational in drug discovery, phenotypic screening, toxicity testing, and vaccine development. Unlike purely biochemical assays, they rely on live cells as the measurement substrate, introducing unique challenges:

• Biological variability and sensitivity of live cells
• Time-dependent viability constraints
• Uniform plating and reproducibility issues
• Environmental requirements (temperature, humidity, CO₂)
• Manual handling limitations, which slow iteration and introduce variability

For many labs, early-stage assay development is less about maximizing throughput and more about ensuring reproducibility and measurement consistency. Typically, only a subset of pre-seeded plates are analyzed to validate robustness or perform pilot dose–response checks before scaling up to high-throughput screening.

Representative System: FlexPod for Cell-Based Assay Development

To address these needs, this representative system was designed around FlexPod, a compact, configurable lab automation platform featuring a mobile design and a collaborative robotic arm. It delivers seamless mobile automation and efficient processing while preserving valuable bench space.  In this case, the FlexPod Platform has been configured to integrate liquid handling, incubation, imaging, and scheduling.  This configuration provides the flexibility to support small-batch, live-cell assay development with unattended, multi-day runs.

Figure 1. Rendering of a representative cell-based assay development FlexPod Configuration which features an Agilent Bravo, LiCONiC STX44, Synentec Cellavista, HighRes Biosolutions LidValets, and more.

Key capabilities include:

• Automated reagent addition or media refeed to pre-seeded plates with the Agilent Bravo
• Controlled incubation with the LiCONiC STX44 for stable temperature, humidity, and CO₂ conditions
• High-content, label-free cellular imaging with the Synentec Cellavista
• Robotic plate transport and lid management using FlexPod with integrated LidValet
• Centralized scheduling and QC of incubation windows and imaging data using CellarioScheduler

One FlexPod customer recently told us:

System Architecture

Figure 2.  Design layout of representative cell-based assay development FlexPod System.

This representative system integrates:

• HighRes FlexPod Platform with dual stackers and barcode scanner
• HighRes LidValet for automated, reliable lid handling
• LiCONiC STX44 standalone incubator (temperature, humidity, CO₂ control)
• Synentec Cellavista high-throughput cellular imaging system
• Agilent Bravo (on-bench liquid handler)
• HighRes 4-position plate hotel for additional labware capacity

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 Example

In a typical assay development cycle, plates move seamlessly between treatment, incubation, and imaging steps under the control of FlexPod and CellarioScheduler, ensuring experiments stay reproducible and on schedule.

1. Cell treatment: Compounds, media, or infections are added to pre-seeded plates using the Agilent Bravo, ensuring precise dosing and consistency across wells.
2. Controlled incubation: Plates are transferred by FlexPod into the LiCONiC STX44 incubator, where temperature, humidity, and CO₂ levels remain tightly regulated to preserve cell viability.
3. Kinetic monitoring: At scheduled intervals, plates are moved to the Synentec Cellavista for high-resolution, label-free imaging to track confluence, morphology, and other phenotypic changes over time.
4. Media refeeding or additional treatments: Automated refeed steps can be scheduled mid-experiment, with FlexPod handling transport and LidValets ensuring clean, contamination-free lid management.
5. Endpoint imaging and data capture: Once the assay has run its course, plates undergo a final imaging step, and data is automatically logged and QC-checked.
6. Integration with LIMS: Through CellarioOS, all imaging, timing, and treatment data are consolidated and can be pushed into external informatics platforms for downstream analysis.

Figure 3. Example cell-based assay development protocol in CellarioScheduler.

With CellarioScheduler, researchers can define precise timing for each step, synchronize incubations and imaging into 24-hour cycles, and run unattended multi-day experiments ensuring both consistency and efficiency.

Software Integration: Future Ready with CellarioOS

The system is designed to integrate seamlessly into CellarioOS, providing:

• Ability to publish protocols with flexibility and simplified ordering
• Full traceability across the entire cell based assay development process
• Access to utilization data
• LIMS integration for data management and reporting

What This Example Shows

By combining liquid handling, incubation, and imaging in a compact footprint, FlexPod enables scientists to iterate rapidly on assay design while ensuring reproducibility. Its modular, mobile format fits alongside standard lab benches and adapts easily as workflows evolve. With robust scheduling and environmental control, this representative system helps assay development teams move from feasibility testing into scalable screening with confidence.

At HighRes, we co-design production-ready workflows that evolve with scientific demand.

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