Chromatography systems

Automation and configurability in FPLC-based protein purification

Cytiva

Sep 15, 2026

Key takeaways

Protein purification is a core task in many labs, but workflows often rely heavily on manual steps, which slows progress, introduces variability, and places excessive burden on experienced staff. These challenges become particularly visible in higher throughput environments, where consistency, speed, and efficient use of time are critical.

Manual handling also increases the risk of sample loss and contamination, especially for sensitive or high-value proteins. As workflows grow in complexity or scale, manual processes can become a bottleneck.

An automated protein purification system based on fast protein liquid chromatography (FPLC) helps address these challenges by improving reproducibility, increasing yields, reducing errors, and protecting samples, while freeing up time for planning and analysis.

Modern FPLC systems are modular, making them easy to configure and extend to meet evolving workflow and user needs.

The value of automation at lab scale

Automation can improve protein purification workflows in several important ways, including:

Reduced hands-on time and fewer manual steps
More consistent runs across users and experiments
Support for multi-step and higher-throughput workflows
Better protection of samples and columns

How automation improves reproducibility and control

Automated FPLC chromatography systems enable continuous monitoring and control of critical purification parameters throughout the run. These include flow rate, column pressure, and air detection. Flow rate affects sample residence time on the resin and directly influences separation performance. Pressure monitoring can help identify issues such as cleaning needs or inadequate sample preparation or sample quality. Air detection prevents air from entering the system flow path and ensures reproducibility, protecting the resin performance and sample recovery.

In addition, automated systems are aware of internal system volumes, ensuring accurate fractionation of your target protein. Together, these capabilities reduce variability between the runs and make purification results more predictable, even as workflows become more complex.

Automated sample handling and loading

Sample handling is often one of the first areas where automation delivers immediate benefits. A dedicated sample pump enables controlled and reproducible sample loading, which introduces samples independently of the main system flow. Autosamplers reduce manual loading and support unattended operation, making them particularly useful for overnight runs or high sample numbers.

Additional components, such as inlet valves, assist in consistent loading and automated cleaning between runs, reduces carryover and protects sample quality. Together these features reduce hands-on time, enabling reliable unattended operation with the built-in security functions and improve repeatability, especially in shared laboratory environments with multiple users.

These capabilities are particularly valuable for automated small scale protein purification, where reproducibility and efficient handling of multiple samples are essential.

Managing workflow flexibility and scale

Flexible valve configurations support multi-step workflows without manual intervention. A modular system design allows valves to be combined and rotated to create different flow paths, enabling the same system to support a wide range of applications. Users can switch between methods, columns, or process steps directly in the software.

This approach supports gradual automation, enabling laboratories to adapt their setup over time, rather than committing to maximum functionality on day one. At the same time, careful system design helps avoid unnecessarily long flow paths that can lead to buffer waste or dilution effects. Features such as reversible flow and well-planned valve layouts help maintain flexibility while preserving performance.

Systems with multiple buffer inlets enable faster buffer changes and more flexible gradients, reducing downtime and simplifying method development.

As automation levels rise and system configurations become more complex, integrated safety features become essential. When these functions are built into the system without adding unnecessary volume to the flow path, they help maintain performance while improving protection. Continuous monitoring of pressure and air helps protect the system, samples, columns, and resins, ensuring reliable performance during unattended runs.

Scalable configurations are particularly valuable in laboratories that frequently move between projects, sample types, or purification scales. Instead of adapting methods to fixed hardware, workflows can be adjusted by rerouting or expanding system components as needed.

Software: The link between hardware and automation

Control software connects all system components, enabling method design, run monitoring, and result analysis from a single interface.

Key software features that support automation:

Intuitive method setup and editing
Real-time run monitoring
Easy access to system and column history
Structured results evaluation and visualization

Traceability tools, such as digital logbooks and sample or column tracking, help maintain consistency, especially in shared labs and regulated environments. Well-designed, user-intuitive software also simplifies user training and reduces variability between operators.

Choosing an FPLC system for automation and future growth

When selecting an FPLC system, it is helpful to consider not only current protein purification workflows but also how workflows may evolve over time. Some systems are well-suited for straightforward, routine purifications, while others are designed to handle more complex methods or future expansion.

When hardware flexibility is combined with software functions such as method queues, automated fraction collection, and unattended runs, hands-on work is reduced and outcomes become more predictable.

Beyond automation level and configuration options, it is also important to consider how the system design affects sample recovery, reproducibility, and method documentation. Poorly optimized system volumes can lead to sample dilution or loss, while robust control and traceable methods help ensure that results can be repeated, clearly described in publications, and used as a reliable guide for future work.

Key questions to consider when choosing an FPLC system are:

How many steps are involved in your typical purification?
Can steps be combined, or do they need to be run separately?
How much manual intervention is required between steps and methods?
Are purification scale or chromatography techniques likely to change over time?
How important are sample recovery, reproducibility, and traceable method documentation for your work?

Conclusion: Building automation that can grow with the lab

Many labs benefit from a phased approach to automation, starting with the most time-consuming or error-prone steps and expanding gradually. A modular and scalable setup allows automation to grow alongside changing research demands, improving throughput and reproducibility without disrupting daily work.

Table 1 below summarizes key aspects and features to consider when evaluating how different configurations support purification workflows.

Table 1. Protein purification needs and features that respond to those requirements.

What do I want to achieve	What it involves	Typical features to be considered
Stable operation, early issue detection, and protection of samples and system components	Continuous monitoring of critical parameters such as flow rate, pressure, and air	Flow control, pressure monitoring, air detection
Support for multi-step workflows and switching between methods without manual intervention	Adjustable flow paths through modular valve setups	Configurable valves, alternative flow paths, inline dilution
Reproducible sample loading, reduced hands-on time, and support for unattended operation	Automated and controlled sample loading and management	Sample pumps, autosamplers
Faster method development, flexible gradients, and reduced downtime	Control and selection of buffers during runs	Multiple buffer inlets, automated buffer switching
Accurate and reproducible fractionation of target proteins	Automated collection and tracking of purified material	Automated fraction collectors, peak-based collection
Consistent performance, easier operation, documentation, and coordination of system configuration	Centralized operation of hardware components and method execution	Method setup, real-time monitoring, digital logbooks
Increased automation level and expanded analytical capabilities	Integration of external devices and extended functionality	Integration of detectors or external modules

Additional resources

Improve protein purification with modular and automated FPLC

Build a more efficient purification workflow with modular FPLC automation designed to improve consistency, reduce manual intervention, and support future expansion.

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