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An Integrated Raman Spectroscopy and Mass Spectrometry Platform to Study Single-Cell Drug Uptake, Metabolism, and Effects
Published on: January 9, 2020
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Towards automation in biologics production via Raman micro-spectroscopy, laser-induced forward cell transfer and
Elisabeth Jaeckle1, Eva Brauchle2, Nadine Nottrodt3
1Fraunhofer Institute for Interfacial Engineering and Biotechnology (IGB), Department of Molecular Biotechnology, Nobelstr. 12, 70569 Stuttgart, Germany.
Journal of Biotechnology
|September 8, 2020
Summary
This study introduces an automated system using Raman spectroscopy and laser-induced forward transfer (LIFT) to identify and separate antibody-producing cells. This innovation streamlines biopharmaceutical production by automating cell line development.
Area of Science:
- Biotechnology
- Biopharmaceutical Manufacturing
- Cell Line Development
Background:
- Mammalian cells are key for biopharmaceutical production due to post-translational modifications.
- Current cell line development is manual, time-consuming, and costly.
- Technical advancements have improved bioprocess efficiency.
Purpose of the Study:
- To develop an automated system for identifying, separating, and characterizing single cell clones for biopharmaceutical production.
- To combine Raman micro-spectroscopy, laser-induced forward transfer (LIFT), and surface-enhanced Raman spectroscopy (SERS).
- To automate manual steps in cell line development for biopharmaceutical manufacturing.
Main Methods:
- Utilized Raman micro-spectroscopy for differentiating antibody-producing and non-producing Chinese Hamster Ovary (CHO) cells.
- Employed laser-induced forward transfer (LIFT) for automated single cell separation and transfer.
- Applied surface-enhanced Raman spectroscopy (SERS) for detecting changes in protein concentration.
Main Results:
- Raman spectra clearly distinguished antibody-producing CHO cells based on human immunoglobulin G (IgG) signals.
- Individual antibody-producing CHO cells were successfully isolated and transferred using LIFT.
- SERS detected concentration changes of human IgG in solution, showing distinct peak intensities.
Conclusions:
- Raman micro-spectroscopy, LIFT, and SERS are effective tools for an automated biopharmaceutical manufacturing system.
- The developed system automates critical steps in cell line development and characterization.
- This approach offers a versatile solution for efficient biopharmaceutical production.

