[论文解读] 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, applications被引用 0

一句话总结

论文提出一种生物兼容的微米尺度DNA水凝胶（microSDs）制备工作流程，具有可调的各向同性膨胀和序列特异性解聚能力，从而实现受控的分子运输并具潜在生物医学应用。

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.

研究动机与目标

• 开发一种生物兼容、材料高效的微尺度DNA水凝胶（microSDs）制备工作流程。
• 实现对各向同性膨胀的模块化控制，膨胀可达到约两倍的尺寸增加。
• 建立定量工作流程以提取有效扩散系数并研究膨胀引起的运输变化。
• 通过序列特异性链置换反应实现microSDs的解溶。

提出的方法

• 生物兼容的制备工作流程，尽量减少死体积和工艺损失。
• 通过模块化DNA序列设计控制microSDs的膨胀行为。
• 使用YOYO-1量化扩散性以及膨胀对球形microSDs分子运输的影响。
• 通过耦合的链置换反应与扩散触发DNA链来实现解溶。
• 分析膨胀引起的网络膨胀作为调控运输特性的机制。

实验结果

研究问题

• RQ1 如何以生物兼容且高效使用DNA的方式制备微尺度DNA水凝胶？
• RQ2 microSDs的各向同性膨胀是否可编程控制，且可达到多大程度？
• RQ3 膨胀如何影响microSDs内的分子运输，如何定量？
• RQ4 microSDs能否被序列特异性的DNA相互作用选择性解溶，动力学受哪些因素支配？

主要发现

• 展示了一种生物兼容、材料高效的microSD制备工作流程。
• 各向同性膨胀可控，通过可编程的DNA设计参数实现膨胀达到约两倍的尺寸增加。
• 使用YOYO-1的定量工作流程量化有效扩散系数与膨胀调控的运输在microSDs中的表现。
• 通过一种DNA链实现microSDs的解溶，解溶动力学由耦合的链置换反应速率和扩散传输共同决定。
• 膨胀引起的网络膨胀能够可预测地调节分子运输，为触发性药物释放和生物传感等潜在应用提供可能。