Multistep genomics on single cells and live cultures in subnanoliter capsules

Publication Summary

Science
December 18, 2025

Authors: Ignas Mazelis, Haoxiang Sun, Arpita Kulkarni, Theresa Torre, and Allon M. Klein

Challenge addressed: Functional genomics is powerful, but most workflows still force a tradeoff: once you process a single cell, you often can’t go back and ask the next question. That’s especially limiting when you want to profile living cells, track changes over time, or run iterative assays on the same cell. In this publication, researchers from Harvard Medical School describe a novel method based on Atrandi's Semi-Permeable Capsule (SPC) technology designed to enable multi-step workflows for living cells.

Major achievement: The team introduces CAGEs (capsules with amphiphilic gel envelopes) and demonstrates proof-of-concept workflows for genome and transcriptome analysis. They also show a live-cell assay that follows gene expression changes – a step toward repeated measurements on the same biological unit.

Role of SPCs: The authors developed their own SPC-like capsules (CAGEs) and analyzed them using Atrandi’s Onyx platform. Onyx supported capsule characterization and workflow development by enabling controlled, high-throughput capsule generation and analysis. The unique advantages offered by this high-throughput capsule handling approach enabled the team to also interrogate individual living cells, which could significantly expand insights into basic biology.

Key quotes: “CAGEs present a powerful tool for live-cell functional and genomic assays,” the team reports. “They will likely enable the profiling of difficult-to-process samples, and may prove useful in studying perturbation outcomes that depend on cell–cell interactions, such as developmental or immune-cell interactions, and for performing colony-forming assays or studies of organoids at scale.”

Read full publication here: https://www.science.org/doi/10.1126/science.ady7209