# Semi-permeable capsules for high-throughput single cell multi-omics

> **NIH NIH R21** · HARVARD MEDICAL SCHOOL · 2022 · $201,306

## Abstract

Project summary
Single cell “multi-omics” represents a promising set of emerging tools to establish crucial links between
transcriptional programs and their underlying drivers such as mutations and the activity of signaling pathways.
These tools have broad application to understand mechanisms of disease, tissue development and
regeneration. The methods involve the simultaneous analysis of the transcriptome of each cell with other
measurements such as DNA sequence, epigenetics and protein composition.
The leading high-throughput paradigms for single cell genomics have technical limitations that severely impact
their use in multiplexing. Only a few genome-wide assays have now been multiplexed at high cell throughput,
and there remains a technical challenge in maintaining good sensitivity upon multiplexing. Some joint
measurements remain undemonstrated and may be impossible to implement with existing methods.
We develop here a novel technology for multi-step biochemical analysis of single cells using sub-nanoliter
semi-permeable compartments (or “capsules”). Capsules should allow multiple complex measurements on
single cells not currently possible, and should improve the quality of data from existing single cell multi-omic
efforts because they overcome the limitations of existing platforms. Cells are captured in capsules in a process
that is cheap and fast, where they may be lysed and barcoded for sequencing. Unlike widely-used methods for
single cell genomics that capture cells in droplets, the capsules are not isolated by oil: instead they exchange
molecules with their environment, which enables multiple reaction buffer exchanges while processing single
cell lysates. Nucleic acids are trapped in capsules without cross-linking. Capsules can also be sorted to allow
screening and enrichment of cell lysates for analysis.
This R21 proposal will bring capsules to practice in single cell multi-omics. It is rooted in preliminary data
where we demonstrate the defining technical requirements of capsules. If successful, this work will establish a
powerful new technology for single cell multi-modal assays that overcomes limitations of existing methods. In
doing so we will implement a multi-omic assay with application to screening and cancer phenotyping, and we
will set the stage for implementing additional high quality multi-omic assays.

## Key facts

- **NIH application ID:** 10569373
- **Project number:** 1R21HG012771-01
- **Recipient organization:** HARVARD MEDICAL SCHOOL
- **Principal Investigator:** Allon Moshe Klein
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $201,306
- **Award type:** 1
- **Project period:** 2022-09-09 → 2024-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10569373

## Citation

> US National Institutes of Health, RePORTER application 10569373, Semi-permeable capsules for high-throughput single cell multi-omics (1R21HG012771-01). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/10569373. Licensed CC0.

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