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Flexible Mechanoporation Chips for High-Throughput Intracellular Delivery Based on Controlled Pneumatic Microvalve
Jianan Qu1, Shuyi Wang1, Chang Chen1
1Department of Mechanics and Engineering Science, College of Engineering, Peking University, Beijing 100871, China.
ACS Nano
|June 12, 2025
Summary
A new flexible mechanoporation chip system enables efficient, high-throughput intracellular delivery of biomolecules into various cell types. This technology minimizes cell damage and addresses challenges in cell manufacturing and therapy.
Area of Science:
- Biotechnology
- Cell Biology
- Bioengineering
Background:
- Mechanoporation offers carrier-free intracellular delivery but faces challenges like size dependence, cellular heterogeneity, and cell damage.
- Existing methods struggle with consistent and efficient delivery across diverse cell populations.
Purpose of the Study:
- To develop and validate a flexible mechanoporation chip system for high-throughput intracellular delivery.
- To overcome limitations of current mechanoporation techniques, enhancing delivery efficiency and minimizing cell damage.
Main Methods:
- Development of a flexible mechanoporation chip integrating a three-layer pneumatic microvalve array.
- Utilizing simulation and experimental data to assess delivery efficiency and cell viability.
- Testing the system's adaptability to varying cell sizes and mechanical properties.
Main Results:
- The system demonstrated minimized cell damage and enhanced delivery efficiency via volume exchange and molecular convection.
- The adaptive microvalve design successfully accommodated cell population variations, optimizing delivery.
- Effective delivery of drugs, mRNA, and plasmid DNA into mouse embryonic fibroblasts, adipose-derived stem cells, and primary T cells was achieved.
Conclusions:
- The flexible mechanoporation chip platform provides efficient, high-throughput, and low-damage mechanical transfection.
- This technology shows significant promise for applications in biomanufacturing, cell therapy, and regenerative medicine.

