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PreprintCC BY-NC-NDbioRxiv

Automated High-Throughput Microfluidic Platform for Cell Pairing and Chemical Fusion

  1. 1School of Engineering and Science, Tecnologico de Monterrey

Abstract

Cell fusion enables cell-based applications, yet systematic optimization remains constrained by low throughput (microfluidic devices) and manual operation (bulk protocols). Here, an automated microfluidic platform is presented for cell pairing and chemical fusion at a statistically relevant scale. High throughput is achieved by arranging ~350,000 deformability-based cell traps as concentric circular arrays in a radial chip. Using tumor and dendritic cells as a model for cancer vaccine, the device reproducibly co-occupies ~75% of traps (~250,000) of which ~140,000 hold exactly one cell of each type. This exceeds the yield of previously reported in hydrodynamic pairing arrays by more than an order of magnitude. A concentration step-up-and-down PEG profile yielded a fusion efficiency of ~20% (range 17.7-23.4%, n =3) at viability above 90% that results in producing at least ~50,000 hybrids per chip. This efficiency is comparable to that reported for PEG-based fusion in small-scale microfluidic devices but obtained at higher throughput and approximately four-fold higher than the conventional benchtop protocol. Fusion efficiencies were quantified by image analysis and validated by flow cytometry. By combining automation, large-area circular trap arrays and reagent control, the platform is useful for data-rich optimization of cell engineering processes previously constrained by limited microfluidic throughput.

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BibTeX
@misc{leon2026automated,
  title = {{Automated High-Throughput Microfluidic Platform for Cell Pairing and Chemical Fusion}},
  author = {R. Silvestre de Leon and E. Gonzalez Gonzalez and R. Rodriguez Moncayo and J. A. Cruz Cardenas and S. Martinez Chapa and J. Voldman and M. Mahdi Aeinehvand},
  howpublished = {bioRxiv},
  year = {2026},
  month = oct,
  doi = {10.64898/2026.10.02.756271},
  url = {https://www.biorxiv.org/content/10.64898/2026.10.02.756271v1},
  note = {CC BY-NC-ND},
}
RIS
TY  - UNPB
TI  - Automated High-Throughput Microfluidic Platform for Cell Pairing and Chemical Fusion
AU  - R. Silvestre de Leon
AU  - E. Gonzalez Gonzalez
AU  - R. Rodriguez Moncayo
AU  - J. A. Cruz Cardenas
AU  - S. Martinez Chapa
AU  - J. Voldman
AU  - M. Mahdi Aeinehvand
PY  - 2026
DA  - 2026/10/02
PB  - bioRxiv
DO  - 10.64898/2026.10.02.756271
UR  - https://www.biorxiv.org/content/10.64898/2026.10.02.756271v1
AB  - Cell fusion enables cell-based applications, yet systematic optimization remains constrained by low throughput (microfluidic devices) and manual operation (bulk protocols). Here, an automated microfluidic platform is presented for cell pairing and chemical fusion at a statistically relevant scale. High throughput is achieved by arranging ~350,000 deformability-based cell traps as concentric circular arrays in a radial chip. Using tumor and dendritic cells as a model for cancer vaccine, the device reproducibly co-occupies ~75% of traps (~250,000) of which ~140,000 hold exactly one cell of each type. This exceeds the yield of previously reported in hydrodynamic pairing arrays by more than an order of magnitude. A concentration step-up-and-down PEG profile yielded a fusion efficiency of ~20% (range 17.7-23.4%, n =3) at viability above 90% that results in producing at least ~50,000 hybrids per chip. This efficiency is comparable to that reported for PEG-based fusion in small-scale microfluidic devices but obtained at higher throughput and approximately four-fold higher than the conventional benchtop protocol. Fusion efficiencies were quantified by image analysis and validated by flow cytometry. By combining automation, large-area circular trap arrays and reagent control, the platform is useful for data-rich optimization of cell engineering processes previously constrained by limited microfluidic throughput.
ER  -