Automated sampling in bioprocesses: SMART study with AMF RVM

Congratulations to Zhi Xian Chan and his team from the Singapore-MIT Alliance for Research and Technology (SMART) for their recent publication in Frontiers in Bioengineering and Biotechnology. Their study introduces a new approach to automated aseptic sampling, showing how this technology can significantly enhance the monitoring of microbioreactors during cell therapy development.

This research is an important milestone: it demonstrates how moving away from purely manual sampling can make bioprocess monitoring more consistent, less error-prone, and scalable, all critical factors in advanced therapies such as CAR-T.

From manual to automated sampling in bioprocess monitoring

Across the field of bioprocessing and biotechnology, the demand for automated sampling systems is rapidly growing. In pharmaceuticals, clinical chemistry, and industrial microbiology, researchers and manufacturers need to collect reliable, representative samples from bioreactors without disrupting the culture. Traditional manual sampling methods, pipettes, syringes, and set-time extractions, are not only labor-intensive but also introduce challenges such as contamination risks, dilution variability, and inconsistent results.

To address these issues, Chan and colleagues developed Auto-CeSS, a specialized automated sampling device capable of extracting very small sample volumes, down to 30 µL, while maintaining sterility. Integrated with both small-scale perfusion microbioreactors and larger well-plate bioreactors, Auto-CeSS enabled continuous monitoring of key metabolites like glucose, lactate, glutamine, and glutamate.

Real-life Auto-CeSS setup with compact footprint, mounted on a mobile trolley. Figure reproduced from Chan et al., Front. Bioeng. Biotechnol., 2025

The results highlight the real advantages of automated sampling: higher efficiency, improved data reliability, and reduced operator workload. Compared to manual sampling, Auto-CeSS ensures reproducible sample collection, supports process analytical technology (PAT), and provides the type of consistent monitoring needed to improve product quality in advanced bioprocess applications.

How the study implemented automated sampling in bioreactors

To put automated sampling into practice, the researchers integrated Auto-CeSS with two distinct bioreactor types: the Breez microfluidic perfusion microbioreactor (2 mL culture volume) and the G-Rex 10M-CS well-plate bioreactor (8 mL culture volume). These systems required aseptic, precise, and repeatable sample collection over multiple days of T-cell culture, making them an ideal testbed for an autosampler device.

Auto-CeSS schematic showing components, fluid pathways, and control modules for automated sampling. Figure reproduced from Chan et al., Front. Bioeng. Biotechnol., 2025

The Auto-CeSS setup was built around a mechanical sampling process that combined pinch valves, a microfluidic peristaltic pump, and a 12-port rotary valve (RVM) from Advanced Microfluidics. This design enabled the system to:

• Switch seamlessly between sampling lines, wash buffers, and waste outlets.
• Direct fluids to multiple microtubes without cross-contamination.
• Minimize dead volume while maintaining aseptic conditions.

The workflow followed a programmed sequence:

1. Priming the sampling line to clear residual fluid.
2. Collecting accurate volumes (30–200 µL, depending on analysis needs).
3. Washing and purging with PBS and sterile air to eliminate dilution variability.
4. Storing each representative sample in separate tubes for downstream analysis.

GUI coding workflow linking user inputs to Arduino for automated sampling with safeguards. Figure reproduced from Chan et al., Front. Bioeng. Biotechnol., 2025

A custom GUI, coded in Python and linked via Arduino, gave researchers easy control over timing and volume. Crucially, the device enabled periodic, automated sampling every 15 minutes, a level of frequency and reliability impossible to achieve with manual sampling methods like pipetting or syringes.

The integration of AMF’s RVM rotary valve allowed multiple sampling ports to be used in parallel, automated waste handling, and ensured each sample remained sterile and isolated. By combining robust hardware, control systems, and aseptic fluid handling, the Auto-CeSS demonstrated how an automated sampling solution can be scaled to support process analytical technology (PAT) and advanced bioprocess monitoring.

Proving the advantages of automated sampling

The study showed that Auto-CeSS delivers reliable and reproducible results when integrated with both small and larger bioreactors.

• Small volumes: The system collected accurate samples as low as 30 µL, making it suitable for microbioreactors with very limited culture fluid.
• High frequency: Automated sampling was possible at 15-minute intervals, something impossible to sustain with manual pipetting.
• Sterility maintained: All samples remained aseptic, confirming the value of a closed-path setup for sensitive cell cultures.
• Comparable quality: Levels of key metabolites, glucose, lactate, glutamine, and glutamate, matched manual sampling, showing no loss of data quality.
• Efficient wash cycles: Using 1000 µL PBS between runs kept cross-contamination below 0.5%.
• Impact on cell growth: Auto-CeSS did not compromise T-cell cultures, with yields of 227 million cells in Breez and 62.6 million in G-Rex.
• Storage effect noted: Some variability in ammonia levels was linked to how samples were stored, underlining the importance of handling conditions.

Comparison of Auto-CeSS automated sampling with manual methods in G-Rex and Breez bioreactors. Data show consistent sample volumes, comparable metabolite profiles (glucose, lactate, glutamine, glutamate, ammonia), and unaffected T-cell growth. Figure reproduced from Chan et al., Front. Bioeng. Biotechnol., 2025

These results confirm that automated sampling can replace manual sampling while improving reliability, sterility, and efficiency, providing laboratories with a practical solution for real-time bioprocess monitoring.

Why the AMF RVM is key to reliable automated sampling

Within the Auto-CeSS is the 12-port Rotary Valve (RVM), which provided the system with its flexibility and precision. More than just a connector, the RVM acted as a sample routing station, enabling controlled fluid handling across multiple outlets.

Its contribution went beyond simple distribution:

• Multi-channel capability: directing samples, wash solutions, and waste streams independently.
• Minimal dead volume: preserving sample integrity and preventing carryover.
• Sterile, closed-path operation: ensuring aseptic conditions for sensitive bioprocesses.
• Integration-ready design: allowing seamless compatibility with peristaltic pumps, syringe pumps, and process analytical technology setups.

This functionality was important for scaling Auto-CeSS from a proof-of-concept into a robust autosampling solution. By automating sample collection, switching, and isolation, the RVM enabled researchers to run multi-day bioreactor monitoring without interruption, while maintaining the accuracy required for metabolite analysis.

The study illustrates how a rotary valve designed for microfluidics can unlock new possibilities for automated sampling systems, making them not just reliable, but also adaptable to a wide range of applications, from bioprocess monitoring to clinical chemistry.

Meet the RVM: a precision rotary valve designed for autosampling

The RVM rotary valve is a purpose-built component for automated fluid handling in microfluidic systems, bioreactors, and bioprocess platforms. Designed for precision and reliability, it is widely used in autosampling setups where sterility, reproducibility, and ease of integration are essential.

RVM series: Industrial Microfluidic Rotary Valve family

Rather than relying on manual sampling methods, pipettes, syringes, or timed extractions, the RVM provides a fully automated approach to sample collection. Its multi-port design enables researchers and engineers to:

• Collect representative samples periodically without disturbing the process.
• Manage sample lines, wash buffers, and waste streams within a single compact unit.
• Maintain a closed, aseptic pathway to protect both product quality and operator safety.
• Integrate seamlessly with syringe pumps, peristaltic pumps, and process analytical technology (PAT) tools for real-time monitoring.

Because it is scalable and versatile, the RVM is used across a wide range of applications, from cell therapy development and bioprocess control to clinical chemistry and analytical instrumentation. In each case, its low carry-over design and robust mechanical performance ensure long-term stability and accuracy.

Key features of the RVM include:

• Compatibility with different automated sampling devices and analytical setups.
• Efficient sample routing that reduces errors, cross-contamination, and manual handling.
• Flexible installation in laboratory or industrial environments, depending on process requirements.

By making fluid handling automation accessible and reliable, the RVM helps laboratories and manufacturers save time, by improving efficiency, and ensuring data quality. Whether implemented as part of a custom autosampler or integrated into larger bioprocess systems, the RVM provides a scalable solution for next-generation automated sampling.

Discover the full publication on automated sampling in cell therapy

The study demonstrates how automated sampling devices can transform bioprocess monitoring by delivering accurate, reproducible, and representative samples directly from a bioreactor. Unlike manual sampling methods that rely on pipettes or syringes and are prone to errors or contamination, the automated approach provides a reliable solution for laboratories working with sensitive cell cultures.

By integrating the Auto-CeSS setup with our 12-port RVM rotary valve, the researchers implemented a mechanical sampling process that enabled precise fluid handling, controlled routing of multiple channels, and sterile sample collection over extended culture periods. This made it possible to monitor critical metabolites in real time, using small volumes while maintaining high data quality.

For laboratories and manufacturers, the advantages of automated sampling systems go beyond efficiency:

• Reliable control and accuracy in sample analysis across a wide range of applications.
• Improved process development through consistent monitoring of bioprocess parameters.
• Scalable integration with existing equipment, including syringe pumps, peristaltic pumps, and analytical instruments.
• Reduced workload and fewer errors compared to manual setups.

The publication underlines how automated autosamplers like Auto-CeSS, powered by AMF’s rotary valve, can support both small-scale and larger systems, providing flexible, efficient, and scalable solutions for next-generation bioprocess automation.

Want to explore the full study and dive deeper into the methods and results?