High-throughput single cell omics using semipermeable capsules

Publication Summary

Science
December 18, 2025

Authors: Denis Baronas, Justina Zvirblyte, Simonas Norvaisis, Greta Leonaviciene, Karolis Goda, Vincenta Mikulenaite, Vytautas Kaseta, Karolis Sablauskas, Laimonas Griskevicius, Simonas Juzenas, and Linas Mazutis

Challenge addressed: Single-cell assays keep getting more ambitious, but many platforms still force a compromise. Droplets are high-throughput, yet difficult to run as true multi-step workflows (washing, buffer exchange, sequential enzymatic steps) or to sort and re-isolate the same single-cell compartments once you’ve started processing. Plates support multistep handling, but sacrifice throughput and scalability. The field needs a way to keep single-cell compartments intact while changing the chemistry around them repeatedly.

Major achievement: In this publication, researchers from Vilnius University and Atrandi Bioscience demonstrate Semi-Permeable Capsules (SPCs) as a practical, scalable single-cell “container” for multi-step biology and show it working in real workflows. They (1) characterize the physical/biochemical behavior of SPCs (including permeability and handling), (2) introduce CapSeq, an SPC-based high-throughput single-cell RNA-seq workflow built around combinatorial barcoding inside capsules, and (3) demonstrate target-driven sorting of SPCs based on RNA signal and later carrying capsules into sequencing, enabling discovery and profiling of rare cell states in complex samples (including patient-derived material).

Role of SPCs: The permeable shell of SPCs is the essential part for scalable multi-step workflows: it keeps cells and large biomolecules contained while allowing small molecules (buffers, enzymes, primers, dyes, nutrients) to diffuse. That means you can wash, exchange reagents, run sequential reactions, and even apply sorting and recovery, without losing single-cell identity. In this article specifically, the biocompatibility of capsules support weeks-long single-cell cultivation and easy enzymatic release, overcoming droplet limitations and simplifying complex workflows like CapSeq. In practice: the compartment stays the same – the chemistry can change.

Key quotes: “Compared with existing droplet-based or microtiter-plate approaches, SPC technology offers larger flexibility and scalability, establishing it as a versatile platform for next-generation single-cell multi-omics research,” the authors conclude.

Read full publication here: https://www.science.org/doi/10.1126/science.ady7227