Solutions for Cell Processing

Importance of the Topic

The development of efficient and noninvasive cell processing methods is critical for advancing regenerative medicine, drug discovery, and biomanufacturing. Establishing genetically uniform cell clones, monitoring culture quality, and characterizing physical properties ensure reproducible outcomes and reduced production costs. Integrating advanced automation and analytical platforms accelerates industrialization of cell based therapies and supports quality control in cell production.

Objectives and Overview of the Study

This whitepaper reviews Shimadzu’s solutions across the cell processing pipeline, from cloning and cell culture to noninvasive evaluation, physical property measurement, and drug discovery support. It aims to demonstrate how each instrument contributes to workflow efficiency, data reliability, and process scalability.

Methodology and Instrumentation

• Automated Clone Picking: CELL PICKER automates colony selection, simplifying manual pipetting and ensuring consistent isolation of genome edited or reprogrammed cells
• Genetic Analysis: MultiNA microchip electrophoresis quantifies DNA and RNA fragments rapidly and accurately
• Mutation Rate Determination: CRISPR–Cas9 cleavage assay coupled with MultiNA electropherogram analysis enables precise calculation of indel frequencies
• Metabolite Profiling: C2MAP system automates pretreatment and LC–MS/MS measurement of up to 95 culture supernatant components
• Metal Content Analysis: AA-7000 atomic absorption spectrophotometer measures trace elements in culture media via flame and graphite furnace methods
• Nanoscale Physical Characterization: SPM-9700HT scanning probe microscope images cell morphology and assesses local mechanical properties in liquid
• Mechanical Testing: MCT micro compression tester quantifies cell mass hardness and deformation under controlled loads

Main Results and Discussion

• CELL PICKER enabled stable and efficient isolation of HCT116 genome edited clones and iPS cell colonies, maintaining undifferentiated marker expression over multiple days
• MultiNA delivered high resolution separation of DNA and RNA fragments, supporting rapid genotyping and indel analysis with minimal hands on time
• C2MAP profiling identified metabolic markers such as kynurenine in undifferentiated iPS cells and 2 aminoadipic acid in ectodermal differentiation, demonstrating noninvasive monitoring of cell state
• AA-7000 AAS detected vendor specific variations in copper, manganese, cobalt, iron, and zinc concentrations in CHO culture media, highlighting the need for trace element control
• SPM imaging revealed differences in cell–cell junction morphology and local stiffness between HeLa and iPS cells; deformation maps correlated with cell elasticity
• MCT measurements quantified significant differences in mechanical strength among HEK293 and two iPS cell lines, indicating potential for physical property based quality assessment

Benefits and Practical Applications

Automation and high throughput analysis reduce manual workload and operator variability, supporting standardized clone generation and quality control. Noninvasive metabolite and metal profiling enable real time monitoring of culture health without consuming precious cell samples. Nanoscale and mechanical assays provide new biophysical quality metrics relevant for tissue engineering and mechanobiology studies.

Future Trends and Potential Applications

• Integration of multiomics and biophysical data with machine learning for predictive quality control
• Real time inline monitoring of bioreactor processes using automated sampling and analysis modules
• Expansion of noninvasive imaging and mechanical testing for organoid and tissue model development
• Standardization of digital twins for cell manufacturing to accelerate scale up and regulatory approval

Conclusion

Shimadzu’s comprehensive suite of automated and high precision instruments addresses critical needs in cell cloning, culture, evaluation, and mechanistic analysis. By combining genetic, metabolic, elemental, and biophysical assessments, these platforms enhance reproducibility, reduce costs, and pave the way for scalable regenerative therapies and advanced biological research.

References

• Yamamoto T, Hatabayashi K, Arita M et al. Kynurenine signaling through the aryl hydrocarbon receptor maintains the undifferentiated state of human embryonic stem cells. Sci Signal 2019;12(590):eaaw3306