# Microfluidic-mass spectrometry analysis of blood–brain barrier transport using engineered microparticle interfaces

## TL;DR

A new microfluidic-mass spectrometry platform enables real-time analysis of blood-brain barrier transport and metabolism using engineered microparticles.

## Contribution

An integrated microfluidic-mass spectrometry platform with engineered BBB particles for dynamic in situ BBB transport and metabolism analysis.

## Key findings

- BBB particles exhibit size- and lipophilicity-dependent permeability and hypoxia-responsive antioxidative protection.
- Chip-MS analysis reveals attenuated efflux of glutamate and lactate, confirming barrier integrity and metabolic regulation.
- The platform provides a scalable and functionally faithful in vitro model for drug screening and neurovascular studies.

## Abstract

The blood–brain barrier (BBB) is vital for maintaining central nervous system (CNS) homeostasis but represents a formidable obstacle to drug delivery, underscoring the need for physiologically relevant in vitro models for CNS drug screening. However, existing in vitro BBB models remain limited in their ability to simultaneously recapitulate multicellular architecture, spatial anisotropy, and dynamic transport behavior while enabling real-time, quantitative analysis. Here, we present an integrated microfluidic-mass spectrometry platform that utilizes engineered BBB particles (BBBps) as a functional analytical interface to enable dynamic, in situ monitoring of BBB transport and metabolism. Using a microfluidic-aerosol hybrid process, we generate multicompartmental microparticles featuring a Matrigel-modified rough surface that enhances endothelial adhesion and tight junction formation, while their cores co-encapsulate microglia, neurons, and astrocytes to establish controlled neurovascular interactions. The BBBps exhibit size- and lipophilicity-dependent permeability, hypoxia-responsive antioxidative protection, and barrier-limited metabolism of salidroside. Real-time analysis with a Chip-MS system further reveals attenuated efflux of glutamate and lactate, confirming barrier integrity and metabolic regulation. This layered design of the micro-blood–brain barrier, combined with Chip-MS analysis, provides a scalable and functionally faithful in vitro model platform for studying drug transport, metabolism, and neurovascular studies.

A barrier-mimetic analytical interface integrating multicellular blood–brain barrier particles with online metabolite detection enables dynamic interrogation of permeability-metabolism coupling for drug screening.