Massively parallel self-assembly of suspendable microcompartments for functional cell screening
6 affiliations
- 1Department of Bioengineering, University of California, Los Angeles, Los Angeles, CA, USA.
- 2Partillion Bioscience Corporation, Los Angeles, CA, USA.
- 3Center for Immunity and Immunotherapies, Seattle Children’s Research Institute, Seattle, WA, USA.
- 4Department of Pediatrics and Pharmacology, University of Washington, Seattle, WA, USA.
- 5California NanoSystems Institute, University of California, Los Angeles, Los Angeles, CA, USA.
- 6Jonsson Comprehensive Cancer Center, University of California, Los Angeles, Los Angeles, CA, USA.
Abstract
Modern biology increasingly demands platforms that can compartmentalize and analyze single cells and cell-cell interactions at massive scale, yet existing compartmentalization strategies based on microfluidics suffer from critical limitations. Emerging lab-on-a-particle technologies such as nanovials enable anchored single cells or small groups of cells to be isolated and assayed in a fully suspendable and parallelized manner using standard instrumentation, although their open architectures can result in loss of growing or un-attached cells. Here, we introduce capped nanovials: self-assembling hydrogel compartments formed by docking spherical capping particles into bowl-shaped nanovials. We routinely achieve capping of >80% of all nanovials in a sample and >90% sorting yield by flow cytometry, making the capped nanovial system well-suited for preparing and running large-scale assays. Furthermore, we demonstrate stable clonal expansion of single mammalian, yeast, and bacterial cells; growth-based selections of >10,000 colonies; enhanced signal-to-noise in secretion assays; and high-purity selection of antibody-secreting cells based on activation of co-encapsulated T cell reporters (>30-fold signal, up to 100% selection purity). By combining the simplicity of a well plate with the functional precision of droplet microfluidics without requiring oil or custom instrumentation, capped nanovials realize accessible, high-throughput, and high-resolution experimentation.
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BibTeX
@article{mellody2026massively,
title = {{Massively parallel self-assembly of suspendable microcompartments for functional cell screening}},
author = {Michael Mellody and Yuta Nakagawa and Alyssa Arnheim and Lily Shang and Catherine Soo and Natalie Tsubamoto and Sarah Taylor and Rajesh Ghosh and Megan Ho and Anna-Marie Guenther and Sumedha Shastry and Wesley Luk and Ian Morales and Jesse Liang and Joseph de Rutte and Richard G. James and Dino Di Carlo},
journal = {Science Advances},
year = {2026},
month = nov,
doi = {10.1126/sciadv.aei7819},
url = {https://www.science.org/doi/abs/10.1126/sciadv.aei7819},
note = {CC BY-NC 4.0},
}
RIS
TY - JOUR
TI - Massively parallel self-assembly of suspendable microcompartments for functional cell screening
AU - Michael Mellody
AU - Yuta Nakagawa
AU - Alyssa Arnheim
AU - Lily Shang
AU - Catherine Soo
AU - Natalie Tsubamoto
AU - Sarah Taylor
AU - Rajesh Ghosh
AU - Megan Ho
AU - Anna-Marie Guenther
AU - Sumedha Shastry
AU - Wesley Luk
AU - Ian Morales
AU - Jesse Liang
AU - Joseph de Rutte
AU - Richard G. James
AU - Dino Di Carlo
PY - 2026
DA - 2026/11/04
JO - Science Advances
DO - 10.1126/sciadv.aei7819
UR - https://www.science.org/doi/abs/10.1126/sciadv.aei7819
AB - Modern biology increasingly demands platforms that can compartmentalize and analyze single cells and cell-cell interactions at massive scale, yet existing compartmentalization strategies based on microfluidics suffer from critical limitations. Emerging lab-on-a-particle technologies such as nanovials enable anchored single cells or small groups of cells to be isolated and assayed in a fully suspendable and parallelized manner using standard instrumentation, although their open architectures can result in loss of growing or un-attached cells. Here, we introduce capped nanovials: self-assembling hydrogel compartments formed by docking spherical capping particles into bowl-shaped nanovials. We routinely achieve capping of >80% of all nanovials in a sample and >90% sorting yield by flow cytometry, making the capped nanovial system well-suited for preparing and running large-scale assays. Furthermore, we demonstrate stable clonal expansion of single mammalian, yeast, and bacterial cells; growth-based selections of >10,000 colonies; enhanced signal-to-noise in secretion assays; and high-purity selection of antibody-secreting cells based on activation of co-encapsulated T cell reporters (>30-fold signal, up to 100% selection purity). By combining the simplicity of a well plate with the functional precision of droplet microfluidics without requiring oil or custom instrumentation, capped nanovials realize accessible, high-throughput, and high-resolution experimentation.
SN - 2375-2548
ER -