Automated high-throughput Raman detection of fluidic samples: measurement setup and methods preventing air bubble...

Area of Science:

• Analytical Chemistry
• Biopharmaceutical Analysis

Background:

• Raman spectroscopy is valuable for biopharmaceutical downstream processing.
• Existing flow cell methods are limited for low-volume samples (<1 mL).
• In-line monitoring struggles with inaccessible sample streams.

Purpose of the Study:

• To develop an automated Raman spectroscopy setup for micro-volume liquid samples.
• To implement methods for mitigating air bubble interference in Raman measurements.
• To enable high-throughput analysis of small sample volumes.

Main Methods:

• Integration of a Tornado Micro Flow Cell with a Tecan liquid handling system via a custom adapter.
• Development of air bubble mitigation strategies: adapted residence time, three-step purging/cleaning, and vertical/upflow orientation.
• Automated sample delivery and Raman spectral acquisition for liquid samples.

Main Results:

• Successful automated Raman measurements with injection volumes as low as 300 µL.
• Demonstrated reduction in air bubble presence and improved spectral robustness.
• Validation of the setup and methods for high-throughput analysis of small fluidic samples.

Conclusions:

• The novel setup and integrated methods enable automated, high-throughput Raman analysis of micro-volume liquid samples.
• Effective air bubble management significantly improves spectral quality and reliability.
• This approach expands the applicability of Raman spectroscopy in biopharmaceutical development and quality control.