# SERSµDrop: A Platform to Study Cell–Cell Communication via SERS Imaging

## TL;DR

SERSµDrop is a new platform that uses Raman spectroscopy to study how breast cancer cells communicate with other cells via extracellular vesicles.

## Contribution

The novel platform combines microfluidic droplets and SERS to monitor EV-mediated communication at single-cell resolution.

## Key findings

- SERSµDrop enables tracking of EV transfer from MCF-7 cells to HDFs over 4 days.
- AuNSt@PA remains intracellular, showing limited exocytic behavior.
- The platform maintains cell viability and allows multiplexed detection.

## Abstract

Cell–cell communication is a fundamental aspect of cellular physiology, with implications in early cancer detection, tumor progression, metastasis, and therapeutic resistance. One key mechanism driving intercellular communication involves extracellular vesicles (EVs), which facilitate the transfer of proteins, lipids, and nucleic acids between cells and play a critical role in modulating tumor behavior. Current tools to study EV‐mediated communication lack the required spatial and temporal resolution to track EV exchange at single‐cell level in physiologically relevant environments. This work introduces SERSµDrop, a microfluidic droplet‐based platform integrating surface‐enhanced Raman spectroscopy (SERS) for high‐resolution monitoring of intercellular communication. In this work we co‐encapsulate MCF‐7 breast cancer cells and human dermal fibroblasts (HDF) in microdroplets and label them with gold nanostars (AuNSt) functionalized with distinct Raman reporters and surface coatings: poly‐l‐arginine hydrochloride (AuNSt@PA) for HDFs, and anti‐CD81 antibodies (AuNSt@AB) to track small EV release from MCF‐7 cells. SERS mapping reveals directional transfer of AuNSt@AB‐tagged EVs from MCF‐7 to HDFs over 4 days, while AuNSt@PA remains intracellular, confirming their limited exocytic behavior. The platform ensures high cell viability, preserves microdroplet integrity, supports high‐throughput screening, and enables multiplexed detection, while minimizing SERS signal dilution through spatial confinement.

SERSµDrop is a microdroplet‐based optofluidic platform that enables real‐time, multiplexed surface‐enhanced Raman spectroscopy (SERS) imaging of small extracellular vesicle‐mediated communication between individual breast cancer and stromal cells. By combining extracellular vesicles labeled with SERS tags, microdroplet confinement, and multivariate spectral analysis, SERSµDrop reveals selective transfer of cellular content from MCF‐7 cells to human dermal fibroblasts within a 3D environment, thereby preserving cell viability and spatial resolution.