# A robust method for on-chip production and manipulation of lipid vesicles by inverted emulsion

**Authors:** Naresh Yandrapalli, David T. Gonzales, Weihua Leng, Cynthia Alsayyah, Nurzhan Abdukarimov, Robert Ernst, T.-Y. Dora Tang

PMC · DOI: 10.1016/j.crmeth.2026.101326 · Cell Reports Methods · 2026-03-10

## TL;DR

A new on-chip method simplifies the production and study of lipid vesicles, avoiding complex equipment and oil layers.

## Contribution

A low-cost, single-chip platform for producing and manipulating lipid vesicles without oil-phase handling or specialized microfluidics.

## Key findings

- The device enables preparation, imaging, and collection of lipid vesicles on a single chip.
- The method avoids contamination and loss by eliminating oil-phase manipulation.
- It supports diverse biochemical assays and synthetic biology applications.

## Abstract

Lipid vesicles are important as minimal model systems for cellular compartmentalization. They drive major advances in deciphering biological mechanisms by molecular reconstitution; provide rational solutions for primitive compartmentalization in origin-of-life studies; form the basis of synthetic cells and drug delivery vehicles. The emulsion method is a well-established route for producing bilayer lipid vesicles. However, the application of this method in microfluidics requires complex and specialized machinery. The bulk method suffers from the need to physically manipulate the vesicles through oil layers for characterization that can damage the vesicles. Given this, we present a facile and robust method for on-chip production and manipulation of lipid vesicles by the emulsion method. We prepared a simple device that allows preparation, imaging, and collection of activated lipid vesicles. This technique combines minimal processing steps with maximum flexibility in lipid vesicle production and manipulation with direct imaging, thus fast-tracking production lines across disciplines.

•A single-chip method for lipid vesicle preparation, manipulation, and imaging•Enables retrieval of vesicles while avoiding the oil phase•Avoids specialized microfluidics and associated shear forces•Low-cost, accessible workflow suitable for broad synthetic biology applications

A single-chip method for lipid vesicle preparation, manipulation, and imaging

Enables retrieval of vesicles while avoiding the oil phase

Avoids specialized microfluidics and associated shear forces

Low-cost, accessible workflow suitable for broad synthetic biology applications

Conventional inverted emulsion methods for the preparation of lipid vesicles are hampered by multiple intervention steps from preparation to characterization and use in assays. We address this problem by developing an inexpensive, easy-to-fabricate device with connected wells on a glass slide that allows for lipid vesicle production, manipulation, and imaging on one chip.

Yandrapalli et al. present an on-chip inverted emulsion method that integrates vesicle production, manipulation, and analysis in one platform without the removal of vesicles through the oil layer. This approach reduces vesicle contamination and loss while enabling diverse biochemical assays, thereby lowering the barriers for synthetic cell and membrane research.

## Full-text entities

- **Chemicals:** Lipid (MESH:D008055), oil (MESH:D009821)

## Full text

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## Figures

5 figures with captions in the complete paper: https://tomesphere.com/paper/PMC13030974/full.md

## References

46 references — full list in the complete paper: https://tomesphere.com/paper/PMC13030974/full.md

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Source: https://tomesphere.com/paper/PMC13030974