# Stable Encapsulation and Responsive Release of Dyes via Noncovalent Molecular Lock Strategy: A Case Study of Rhodamine B Based Fluorescent Hydrogel Microspheres

## TL;DR

This paper introduces a new method to create fluorescent microspheres that can stably hold dyes and release them under specific conditions, useful for tracking fluid flow.

## Contribution

A novel noncovalent molecular lock strategy is developed for stable dye encapsulation and controlled release in hydrogel microspheres.

## Key findings

- PEGDA@RhB-TA microspheres retain RhB in salt and heat conditions but release it rapidly in ethanol-water mixtures.
- TA forms noncovalent interactions with RhB, acting as a molecular lock to control dye release.
- The microspheres enable accurate flow velocity measurements in microfluidic systems.

## Abstract

Hydrogel fluorescent microspheres function as versatile tracers with applications spanning across biomedicine, complex plasma systems, hydrodynamics, and drug delivery. However, the controlled release of fluorescent material in hydrogel microspheres is challenging to achieve. The fluorescent hydrogel microsphere (namely poly(ethylene glycol) diacrylate@rhodamine B-tannic acid, PEGDA@RhB-TA) was fabricated by incorporating tannic acid and RhB into PEGDA microspheres. The stable encapsulation and responsive release of RhB can be achieved by leveraging the non-covalent interactions between TA and RhB. RhB was stably encapsulated within PEGDA microspheres through noncovalent interactions (hydrophobic interactions, hydrogen bonding, π–π, and ion–π interactions) between RhB and TA. Both molecular dynamics simulations by GROMACS and experimental results confirmed the noncovalent binding mechanisms between RhB and TA. The microspheres retained RhB following 24 h immersion in a highly concentrated salt solution (1 M NaCl) and exhibited minimal RhB release (7.1%) under heating at 80 °C for 24 h. However, PEGDA@RhB-TA microspheres underwent rapid RhB release in a 50% v/v ethanol–water solution, liberating 73% of the encapsulated dye within 24 h. TA within the PEGDA@RhB-TA microsphere acts as a molecular lock by forming non-covalent interactions with RhB, significantly enhancing the stability of encapsulated RhB, and enabling the responsive release of RhB under specific conditions. Upon introduction into a microfluidic chip, PEGDA@RhB-TA microspheres enable the calculation of flow velocity through position tracking using high-speed camera imaging and fluorescence microscopy. These microspheres overcome the dual challenges of tracer stability and controlled release, making them suitable for fluid tracing and measuring flow rates.