Stem cells hold incredible potential in regenerative medicine, offering promise for treating a wide range of diseases. However, turning this potential into reality is a challenging process that involves overcoming numerous technical hurdles, including the need for efficient, scalable, and cost-effective cell production. This is where automation can play a crucial role, enabling researchers to achieve consistent results while scaling up production for industrial and therapeutic applications.

Why Automation in Stem Cell Workflows?

Historically, stem cell research has relied heavily on manual techniques. This requires highly skilled labor and is prone to contamination, variability, and scalability issues. Manual cell culture can be highly time-consuming and labor-intensive, limiting the number of experiments that can be performed and restricting the throughput needed for large-scale research projects or clinical applications. For instance, in the study by Truong et al. (2021), an automated platform (TECAN Fluent) was used to culture and differentiate human induced pluripotent stem cells (hiPSCs) into retinal pigment epithelium (RPE). This automated approach enabled reproducible, and scalable generation of RPE cells, illustrating the potential for automation in personalized drug testing and disease modeling for age-related macular degeneration (AMD) patients. A similar approach can be implemented virtually on any other liquid handling robots such as Hamilton.

The Benefits of Automation in Stem Cell Culture

There are multiple advantages to integrate automation in cell culture workflow which I listed a few key ones with examples from recent publications below:

1. Enhanced Efficiency and Throughput: Automated systems can perform routine tasks such as media changes, cell seeding, and harvesting at a faster pace and with higher precision than manual methods. For example, Bando et al. (2022) introduced a compact, automated culture machine designed for maintaining and differentiating hiPSCs. This system successfully expanded hiPSC cultures under feeder-free conditions and simultaneously differentiated them into cardiomyocytes, hepatocytes, neural progenitors, and keratinocytes. This machine uses a novel x-y-z-axes-rail-system to perform automated cell culture processes, making it easier for research laboratories to adopt iPSC-based workflows without the need for extensive space or specialized training. This level of automation reduces the need for highly trained personnel and supports high-throughput screening in various research fields.
2. Improved Reproducibility and Consistency: One of the main advantages of automation is its ability to reduce variability and human error. This is particularly important in stem cell research, where even small variations in culture conditions can significantly impact cell behavior and differentiation outcomes. Automating these processes ensures that experiments are reproducible and results are consistent across different batches and laboratories.
3. Reduced Contamination and Safety Risks: Automation minimizes human intervention, thereby reducing the risk of contamination and exposure to hazardous materials. This is especially important when working with stem cells for clinical applications, where sterility and safety are paramount.
4. Scalability for Large-Scale Production: Automated systems can easily be scaled up to handle large numbers of cell cultures and experiments simultaneously. This capability is essential for translating stem cell research from the lab to the clinic and supporting commercial-scale production of cell therapies. Elanzew et al. (2020) reported the development of the StemCellFactory, a modular platform that covers the entire hiPSC production workflow, from reprogramming human fibroblasts to expanding hiPSC clones. The platform integrates advanced hardware and software components, enabling parallel processing of multiple hiPSC lines and providing a scalable solution for disease modeling and drug screening.

Figure 1. The StemCellFactory, an automated system for reprogramming and expansion of iPSCs. From DOI: 10.3389/fbioe.2020.00811

Market Trends, Future Directions, and Challenges

As the demand for stem cell therapies and personalized medicine grows, the market for automated cell culture systems is expected to expand rapidly. The global automated cell culture market was valued at USD 18.75 billion in 2023 and is projected to reach USD 47.50 billion by 2032, growing at a compound annual growth rate (CAGR) of 11.28%. This growth is driven by increasing adoption of automated technologies in both research and industrial settings. As automation platforms become more accessible, modular, and user-friendly, they will likely play a critical role in enabling the widespread adoption of stem cell technologies for clinical and commercial applications.

Despite the numerous benefits, there are still challenges to the widespread adoption of automation in stem cell research. Setting up automated systems can be expensive, especially for smaller research laboratories. In addition, operating and maintaining automated systems requires specialized knowledge and skills. Researchers may need additional training to fully utilize the capabilities of these systems. The other challenge is to integrate automation when the lab is already using manual techniques. However, the long-term benefits in terms of reduced labor costs and increased efficiency often justify the investment.

Figure 2. Schematic representation of novel or facilitated applications for hPSCs by automation. From DOI: 10.1177/247263031771222

Conclusion

The automation revolution in stem cell research is transforming the field by enabling high-throughput, reproducible, and scalable workflows. From compact, automated culture machines to large-scale platforms like the BioNex Solution’s Hive and CELLITRO RoboCell, automation is addressing the challenges of manual cell culture and making stem cell research more accessible and effective. As these technologies continue to evolve, they will play an increasingly important role in translating the promise of stem cells into real-world therapies and clinical applications.

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The main event of the Society for Laboratory Automation and Screening (SLAS) is its annual International Conference and Exhibition which rotates between Boston and San Diego. If you are new to SLAS, I highly recommend visiting their expo which you can purchase 1-day or three-day passes for a relatively low price (<300$). As a pro tip, you can most likely get free guess passes from your lab suppliers, especially those related to lab automation or high-throughput instruments. This year (2024) SLAS was February 3-7, 2024 at the Boston Convention and Exhibition Center. https://www.slas.org/events-calendar/slas2024-international-conference-and-exhibition/ I am going to capture a few observations from 1-day my visit here.

Something I noticed in the Expo hall was the growing trend of specialized affordable small liquid-handling robots. These are benchtop robots with less flexibility which are designed to execute a particular task, such as PCR plate setup, and nucleic acid extraction. Macherey-Nagel isoPure mini and MagBinder from Omega-Bio tek are designed for magnetic-bead-based nucleic acid extraction of 1-24 samples. The other system was Myra from BMS which can prep reaction tubes to use with their MIC qPCR. One more flexible system is the Hamilton Microlab Prep. It costs $20-30k and can have up to two independent 8-prob heads. It controls with an integrated tablet and an App-like software. There are also a few devices (heat, cooler, shaker) and accessories (reservoirs, tube, and plate adapters) available that can improve the versatility of the system. It has a limited working deck (9 positions) but I recommend checking it if you are looking to introduce automation to your workflow. It can be a great option for simple tasks such as plate prep, serial dilutions, transfer, and cherry-picking. https://www.hamiltoncompany.com/automated-liquid-handling/platforms/microlab-prep

Figure 1. Example of small footprint robots in SLAS2024 that can simplify low throughput specialized applications.

The other interesting innovations were around total lab automation. Biosero Omron is a mobile robot that can move labware between workstations with equipment spread throughout the laboratory, across multiple floors, or even different buildings. Mobile robots can enhance the modality and flexibility of the workflow but would need designated infrastructure and a high level of integration. Nonetheless, it is exciting to see a robot moving a microplate from an incubator to a centrifuge across the room!

There were also a few floating transport systems that combined the advantages of conventional systems and supplemented them with a unique magnetic levitation technology. With their floating 2D transport, they can rotate, tilt, and elevate microplates which opens up a whole host of new possibilities. For instance, Hamilton integrated a Beckhoff XPlanar with a Vantage system (called Vantage Plus) to virtually extend the deck in any direction. Planar Motors was another vendor that offered similar technology.

Figure 2. Two examples of technologies that enable across-lab integration.

The other boosts that catch my eyes were CELLTRIO and BioNex which offer highly integrated enclosed robotic systems. These systems are usually cost-prohibitive for most applications. However, they are valuable tools for multi-step applications that are laborious, delicate, and need a sterile environment, such as cell-based processes.  CELLITRO RoboCell Cell Line Automation Platform performs cell maintenance, culture, passage, differentiation, transformation, cell line development, biobanking, assays, imaging, and screening for multiple cell lines such as adherent, suspension, primary, immortalized, iPSC. The platform can handle various flask types, plates, and even serological pipettes. https://celltrio.com/

BioNex Solution’s Hive Automation Platform uses vertical space to facilitate the integration of a large number of instruments and consumable storage in a relatively small footprint.  Vertical design facilitates compact system integration of BioNex instruments with third-party devices without compromising performance. One key technology is their BumbleBee sample handler that provides independent channels and rotating sample translators enabling fast, simultaneous picking from and placing any location on the sample deck.  https://bionexsolutions.com/

Multiple vendors offered OEM services, custom-made instruments/robots, data infrastructure, scheduling software, and more liquid handling system options. One liquid handling system that I saw in several boosts was Lynx from Dynamic Devices. I have not used their system, but seems they are growing in popularity probably due to their Volume Verified Pipetting (VVP) technology. Anyway, it is always enticing to visit SLAS Exhibitions!

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Figure 3. BioNex Solution’s Hive Automation and CELLITRO RoboCell Cell Line Automation platforms offer highly integrative systems for cell and other biological applications.