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Background <p>Chimeric antigen receptor T (CAR-T) cell therapies have transformed the treatment landscape for hematological malignancies, yet their large-scale manufacturing still faces significant technical, economic, and regulatory constraints. Microfluidic-mediated mechanical poration (MMP) has emerged as a promising non-viral strategy for intracellular delivery in cell engineering, offering high-throughput operation, reduced reagent consumption, and the possibility of preserving cell viability compared with conventional physical delivery methods.</p> Main body <p>This review provides a structured assessment of the main MMP modalities, including constriction-based squeezing, volume exchange convective transfection (VECT), vortex shedding, spiral/viscoelastic hydroporation, and droplet mechanoporation, highlighting how device geometry, flow regime, and deformation mechanism influence delivery efficiency and cell integrity. Across the studies analyzed, reported delivery efficiencies frequently range from 60% to &gt;95%, with cell viabilities commonly above 80–90% and processing capacities reaching from approximately 1 × 10<sup>6</sup> to 2.5 × 10<sup>8</sup> cells/min, depending on the device design, cargo, cell type, and operating conditions. Compared with viral vectors, MMP avoids complex vector production and may reduce biosafety and manufacturing burdens, while compared with electroporation, it may offer advantages in continuous-flow processing, cytotoxicity reduction, and cell recovery.</p> Conclusions <p>Microfluidic-mediated mechanical poration shows strong potential as a next-generation intracellular delivery strategy for CAR-T cell manufacturing, combining efficiency, scalability, and reduced cytotoxicity. However, the current evidence remains uneven: many studies still rely on model cell lines or surrogate cargos, and direct validation in primary human T cells using CAR-encoding mRNA, DNA, or CRISPR-Cas9 components remains limited. Further optimization, regulatory alignment, and GMP-compatible integration are required to translate MMP from high-performing laboratory prototypes into reliable components of next-generation CAR-T cell manufacturing workflows.</p> Graphical Abstract <p></p>

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Microfluidic platforms for CAR-T cell engineering: a multidisciplinary review on potential next generation intracellular delivery method

  • 期刊论文

  • 出版模式：

    开放获取

  • 发表日期：

    2026年7月29日

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  • Isabela Aparecida de Araujo Andreotti,
  • Gabriel Griep,
  • Edgar Andrés Patiño Nariño,
  • Leonardo Ribeiro Batista-Silva,
  • Mario Ricardo Góngora-Rubio,
  • Martín Hernán Bonamino,
  • Tiago Albertini Balbino

摘要

Background

Chimeric antigen receptor T (CAR-T) cell therapies have transformed the treatment landscape for hematological malignancies, yet their large-scale manufacturing still faces significant technical, economic, and regulatory constraints. Microfluidic-mediated mechanical poration (MMP) has emerged as a promising non-viral strategy for intracellular delivery in cell engineering, offering high-throughput operation, reduced reagent consumption, and the possibility of preserving cell viability compared with conventional physical delivery methods.

Main body

This review provides a structured assessment of the main MMP modalities, including constriction-based squeezing, volume exchange convective transfection (VECT), vortex shedding, spiral/viscoelastic hydroporation, and droplet mechanoporation, highlighting how device geometry, flow regime, and deformation mechanism influence delivery efficiency and cell integrity. Across the studies analyzed, reported delivery efficiencies frequently range from 60% to >95%, with cell viabilities commonly above 80–90% and processing capacities reaching from approximately 1 × 106 to 2.5 × 108 cells/min, depending on the device design, cargo, cell type, and operating conditions. Compared with viral vectors, MMP avoids complex vector production and may reduce biosafety and manufacturing burdens, while compared with electroporation, it may offer advantages in continuous-flow processing, cytotoxicity reduction, and cell recovery.

Conclusions

Microfluidic-mediated mechanical poration shows strong potential as a next-generation intracellular delivery strategy for CAR-T cell manufacturing, combining efficiency, scalability, and reduced cytotoxicity. However, the current evidence remains uneven: many studies still rely on model cell lines or surrogate cargos, and direct validation in primary human T cells using CAR-encoding mRNA, DNA, or CRISPR-Cas9 components remains limited. Further optimization, regulatory alignment, and GMP-compatible integration are required to translate MMP from high-performing laboratory prototypes into reliable components of next-generation CAR-T cell manufacturing workflows.

Graphical Abstract