[Paper Review] Microfluidic Fabrication and Analysis of Biocompatible, Monodisperse DNA-Hydrogels with Tunable Swelling and Dissolution Kinetics

Corinna Torabi, Takayuki Suzuki+5 more|arXiv (Cornell University)|Jan 28, 2026

Hydrogels: synthesis, properties, applications0 citations

TL;DR

The paper presents a biocompatible fabrication workflow for micron-scale DNA hydrogels (microSDs) with tunable isotropic swelling and sequence-specific dissolution, enabling controlled molecular transport and potential biomedical applications.

ABSTRACT

Stimulus-responsive DNA-hydrogels with swelling capabilities are a promising class of materials for biomedical applications such as drug delivery and biosensing. Designing these systems remains challenging because fabrication methods must be simultaneously biocompatible and conserve scarce DNA materials, even at the microscale. Moreover, stimulus-induced swelling must be precisely controlled and shown to drive measurable changes in molecular properties. We present a biocompatible fabrication and characterization method for micron-scale DNA-hydrogels with tunable isotropic swelling and dissolving properties. We first developed a fabrication method demonstrating that both the hydrogel composition and the fabrication process itself are biocompatible, while also minimizing the consumption of valuable DNA reagents. We then demonstrated modular control over isotropic swelling in micron-scale DNA microgels, achieving up to a two-fold size increase with tunable swelling through defined design parameters. We further established a quantitative workflow to measure structural changes of spherical, swollen and unswelled microgels leveraging the diffusive properties of a DNA-binding dye. Finally, we demonstrate tunable dissolving of microgels and quantitatively reveal various experimental factors that influence dissolution rates beyond what is traditionally considered in microgel experiments. Together, these advances establish a biocompatible platform for the fabrication and analysis of stimulus-responsive DNA micro-hydrogels, providing a foundation for their future use in drug delivery, biosensing, and related biomedical technologies.

Motivation & Objective

• Develop a biocompatible, material-efficient fabrication workflow for microscale DNA hydrogels (microSDs).
• Achieve modular control over isotropic swelling up to a two-fold size increase.
• Establish a quantitative workflow to extract effective diffusivity and study swelling-induced transport changes.
• Demonstrate dissolution of microSDs via sequence-specific strand-displacement reactions.

Proposed method

• Biocompatible fabrication workflow that minimizes dead volume and process loss.
• Modular design of DNA sequences to control swelling behavior in microSDs.
• Use of YOYO-1 to quantify diffusivity and swelling effects on molecular transport in spherical microSDs.
• Dissolution triggered by a DNA strand through coupled strand-displacement reactions and diffusion.
• Analysis of swelling-induced network expansion as a mechanism to modulate transport properties.

Experimental results

Research questions

• RQ1 How can micro-scale DNA hydrogels be fabricated in a biocompatible and DNA-efficient way?
• RQ2 Can isotropic swelling of microSDs be programmably controlled, and by how much?
• RQ3 How does swelling affect molecular transport within microSDs, and how can it be quantified?
• RQ4 Can microSDs be selectively dissolved by sequence-specific DNA interactions, and what governs the kinetics?

Key findings

• A biocompatible, material-efficient fabrication workflow for microSDs was demonstrated.
• Isotropic swelling was controllable, achieving up to a two-fold size increase through programmable DNA design parameters.
• A quantitative workflow using YOYO-1 quantified effective diffusivity and swelling-modulated transport in microSDs.
• Dissolution of microSDs was achieved using a DNA strand, with dissolution kinetics governed by coupled strand-displacement reaction rates and diffusive transport.
• Swelling-induced network expansion enables predictable modulation of molecular transport, enabling potential applications in triggered drug delivery and biosensing.