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High-throughput Protein Expression Generator Using a Microfluidic Platform
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An automated modular microfluidic platform for end-to-end mRNA synthesis and purification.

Vikas Sharma1, Amirreza Mottafegh1, Jeong-Un Joo1

  • 1Center for Intelligent Microprocess of Pharmaceutical Synthesis, Department of Chemical Engineering, Pohang University of Science and Technology (POSTECH), Pohang 37673, Republic of Korea. dpkim@postech.ac.kr.

Lab on a Chip
|April 14, 2026
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Summary

This study presents an automated microfluidic platform for mRNA production, integrating transcription with purification. The new system significantly increases mRNA yield and purity compared to traditional batch methods, reducing manual labor.

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Area of Science:

  • Biotechnology
  • Chemical Engineering
  • Molecular Biology

Background:

  • Manual downstream processing in microfluidic mRNA synthesis hinders production scalability.
  • Existing methods require significant manual intervention, acting as a bottleneck for practical applications.

Purpose of the Study:

  • To develop an end-to-end, automated microfluidic platform for integrated mRNA synthesis and purification.
  • To overcome the limitations of manual batch operations in microfluidic in vitro transcription (IVT) workflows.

Main Methods:

  • Integration of an oscillatory microfluidic IVT (Os(IVT)) module with microfluidic digestion/clarification (μFD) and multimodal chromatography (MMC) units.
  • Utilized immobilized DNase I for template removal and micro-tangential flow filtration (μ-TFF) for buffer exchange and clarification.
  • Employed real-time feedback control (pH, conductivity) for automated chromatography in the MMC module.

Main Results:

  • Achieved a 2-hour synthesis-to-purification workflow for mRNA.
  • Produced approximately 2.0x higher mRNA yield (1275 ± 1.7 μg) compared to batch methods (641 ± 0.6 μg).
  • Demonstrated ~93.3% MMC recovery and an 83.3% reduction in dsRNA impurities.

Conclusions:

  • The developed platform transforms microfluidic IVT into a closed-loop manufacturing system.
  • Enables rapid, reproducible, and high-quality mRNA production with minimized manual handling.
  • Advances microfluidic technology for scalable biomanufacturing applications.