Automated stem cell culture for high-content drug discovery

This article and associated images are based on a poster originally authored by Isabel Gameiro-Ros, Denise R B de Pilger, Ming Jiang, Ok-Ryul Song, Scott Warchal, Christophe Queval, Adrien Pasquier, Joseph Tuersley, Harry Saville, John Hellicar, Sara Tamagno and Michael Howell and presented at ELRIG Drug Discovery 2026 in affiliation with The Francis Crick Institute.

This poster is being hosted on this website in its raw form, without modifications. It has not undergone peer review but has been reviewed to meet AZoNetwork's editorial quality standards. The information contained is for informational purposes only and should not be considered validated by independent peer assessment.

Overview

Human induced pluripotent stem cells (iPSCs), embryonic stem cells (ESCs), and 3D organoids are becoming foundational models in drug discovery. They provide authentic, experimentally accessible human cells and improve the translational relevance of target and compound discovery. However, using them at scale remains difficult. Maintaining these cultures needs considerable technical skill and staff commitment, an estimated 10-20,000 hours per year across Crick stem cell researchers, and complex manipulations such as differentiations can demand up to 30 days of continuous activity. Manual handling also adds batch-to-batch and user-related variability that carries through into downstream assays.

To overcome these limitations, we developed integrated automated platforms that connect robust stem cell culture with genetic engineering, complex cell-based assays, and high-throughput screening. Here we show how automation can:

• Maintain multiple ES/iPSC lines long-term with minimal manual intervention
• Support CRISPR engineering and functional screening
• Enable multiplexed and continuous high-throughput screening on stem cell-based models

What an automated and integrated workflow enables

1. Automated ES/iPSC culture: Single-cell and clump passaging, long-term, standardized and monitored.
2. Robust QC of stem cells: Ensure ES/iPSCs maintain quality standards in automated culture.
3. Genetic engineering: CRISPR-based cell line engineering.
4. High-throughput screening: CRISPR KO/overexpression, small molecule and siRNA screens.
5. Downstream models: Stem cell differentiation and organoid generation.

Infrastructure: Automated platforms

1. Automated stem cell culture

The platform consists of multiple devices that interact with each other and communicate via Momentum scheduling software. Robotic handling, automated liquid handling, incubation, and imaging enable long-term, standardized maintenance of multiple human ES/iPSC lines with minimal manual intervention. Our workflows support both single-cell and clump passaging, with automated monitoring of culture quality and cell state through live imaging.

2. Supporting automated infrastructure

• Liquid handling: Our portfolio (Echo, Combi nL, Myra, Biomek FX, Multiflo and Viaflo) lets us run complex cell-based and other assays in a range of plate formats (24- to 384-well) and volumes (nL to mL).
• Automated microscopes: Our imaging resources span from low-resolution live-cell imaging over several days to spinning-disk confocal microscopes (e.g., Opera Phenix Plus) coupled to robotic systems, capable of continuous and autonomous image acquisition and analysis.
• Automated analysis pipelines: Quantification of stem cell properties and cell line-specific characteristics of stem cell-based models.
• Database reference: Benchmark data mapped to internally established and standardized stem cell quality criteria.

Fig 2. Example of one of our automated microscopes and stem cell models generated in collaboration with Crick’s research groups. Image Credit: Isabel Gameiro-Ros et al., in partnership with ELRIG (UK) Ltd.

3. Stem cell-based 3D model systems

Our automated platforms are not confined to adherent cells. We also help research groups use them for 3D model systems, where they can support the maintenance, monitoring, and experimental manipulation of organoids, gastruloids, and cancer spheroids.

Fig 3. Brightfield images of trunkoids (days 0-3). In collaboration with Tiago Rito (Briscoe lab). Image Credit: Isabel Gameiro-Ros et al., in partnership with ELRIG (UK) Ltd.

Results: Quality and reproducibility of automated stem cell cultures

1. Pluripotency and genomic stability

Across 16+ passages, automated ES and iPSC cultures maintained genomic stability, > 95% expression of pluripotency markers, and robust trilineage differentiation capacity. STR profiling and mycoplasma testing confirmed the identity of all cell lines and the absence of contamination, respectively.

2. Differentiation capability

Fig 5. We used the STEMdiff^™ Trilineage Differentiation Kit to compare the differentiation of Wibj2 iPSCs cells using the automation system and the manual method, obtaining similar results for both approaches: All three germ layers presented an elevated expression of specific markers for early differentiation and low expression of the undifferentiated marker OCT3/4. Image Credit: Isabel Gameiro-Ros et al., in partnership with ELRIG (UK) Ltd.

Conclusions

Our automated stem cell platform turns labor-intensive stem cell and complex cell-based workflows into a scalable resource for discovery research as well as drug and target discovery.

Automated cultures maintain genomic stability, pluripotency, and trilineage capacity over 16+ passages while cutting hands-on time by up to 85%.

Over 85% less hands-on researcher time

8 x 12-well plates, 4 cell lines, passaging every 4 days for 9 weeks

Image Credit: Isabel Gameiro-Ros et al., in partnership with ELRIG (UK) Ltd.

Our integrative approach, coupling automated stem cell culture with automated data analysis and quantification, allows us to streamline and positively contribute to the growing field of stem cell research.

Acknowledgments

We thank the Wolfson Foundation for funding the automated stem cell culture platform.

We also thank the Stem Cell and Automation Platform (SCOP) and the Genomics Science Technology Platform at the Francis Crick Institute for their collaboration on this work.

Download the original poster

About The Francis Crick Institute

The Francis Crick Institute is dedicated to understanding the fundamental biology underlying health and disease. Our work is helping to understand why disease develops and to translate discoveries into new ways to prevent, diagnose and treat illnesses such as cancer, heart disease, stroke, infections and neurodegenerative diseases.

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Last Updated: Oct 30, 2026