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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
PubMed
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.

Keywords:
cell deformationflexible mechanoporationintracellular deliverymechanobiologytransfection

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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.