Solutions for Cell Processing

Importance of Topic

Cell research and production underpin modern regenerative medicine and biopharmaceutical manufacturing.
Accurate identification, cultivation and evaluation of cell lines is essential for ensuring reproducible quality and safety.
Automation and non-invasive analytical methods can accelerate workflows and reduce costs while preserving cell integrity.

Objectives and Overview

This article reviews Shimadzu’s integrated solutions for cloning, culture, non-invasive evaluation and physical property analysis of cells.
It covers automated colony picking, DNA/RNA sizing, media component profiling, metal element detection, and biomechanical measurement platforms.
The goal is to highlight technologies that streamline clone strain establishment, monitor cell growth, and characterize functional properties.

Methods and Instrumentation

• CELL PICKER Automated Colony Collector: robotic pipette-based platform for high-precision isolation of gene-edited or reprogrammed cell clones under microscopic control.
• MultiNA Microchip Electrophoresis: fully automated DNA/RNA sizing and quantification system with high resolution and throughput up to 120 samples.
• C2MAP Cell Culture Media Analysis Platform: LC-MS/MS pipeline for non-invasive monitoring of up to 95 medium components and secreted metabolites with automated sample prep.
• AA-7000 Atomic Absorption Spectrophotometer: flame and graphite furnace-based analysis of trace metal elements in culture media with minimal sample preparation.
• SPM-9700HT Scanning Probe Microscope: nanoscale mapping of cell surface topography and local mechanical properties in liquid environments.
• MCT Series Micro Compression Tester: precise measurement of force-displacement curves and hardness of three-dimensional cell aggregates.

Main Results and Discussion

• CELL PICKER achieved reliable isolation and expansion of genome-edited HCT116 and iPS cell colonies, maintaining marker expression and viability over six days.
• MultiNA was used to calculate CRISPR-Cas9 mutation rates via analysis of cut and uncut PCR fragments, enabling rapid genotyping of edited cell populations.
• C2MAP identified dynamic changes in tryptophan and kynurenine levels correlating with iPS cell undifferentiation, and discovered 2-aminoadipic acid as an ectoderm differentiation marker.
• AA-7000 AAS detected vendor-specific variations in copper, manganese, cobalt, iron and zinc concentrations in CHO culture media, informing quality control strategies.
• SPM-9700HT mapped distinct mechanical profiles of HeLa and iPS cells, revealing uniform hardness in tumor cells versus heterogeneous rigidity in stem cells.
• MCT Series differentiated mechanical strengths of HEK293 and two iPS cell aggregates, demonstrating a quantitative method to assess tissue stiffness.

Benefits and Practical Applications

• Automation reduces manual labor and operator bias, enhancing throughput and reproducibility in clone selection and media analysis.
• Non-invasive assays preserve living cultures, enabling longitudinal monitoring of growth, differentiation and metabolic activity.
• Integration of physical property measurement provides novel biomechanical biomarkers for cell line quality and tissue engineering.
• Trace metal profiling supports consistent culture conditions for biopharmaceutical manufacturing and regenerative medicine processes.

Future Trends and Possibilities

Cell processing is moving towards fully integrated, data-rich workflows combining genomics, metabolomics and biomechanics.
Real-time monitoring with minimal sample handling will facilitate adaptive control of culture environments.
Machine learning applied to multi-parameter datasets can predict cell behavior and process outcomes.
Miniaturization and parallelization will further boost throughput for personalized cell therapies and high-content drug screening.

Conclusion

Shimadzu’s suite of automated instrumentation addresses critical bottlenecks in cell line development, culture monitoring, and advanced characterization of living cells.
These solutions improve efficiency and data quality while minimizing invasive sampling, paving the way for robust industrial-scale cell manufacturing and regenerative therapies.

Reference

• Takako Yamamoto et al., Sci. Signal. 12, eaaw3306 (2019)