Koball Andrea, Obst Franziska, Gaitzsch Jens, Voit Brigitte, Appelhans Dietmar
Leibniz-Institut für Polymerforschung Dresden e.V., Hohe Straße 6, D-01069, Dresden, Germany.
Technische Universität Dresden, Fakultät Chemie und Lebensmittelchemie, Organische Chemie der Polymere, D-01062, Dresden, Germany.
Small Methods. 2024 Dec;8(12):e2400282. doi: 10.1002/smtd.202400282. Epub 2024 Jul 11.
Microfluidic flow reactors permit the implementation of sensitive biocatalysts in polymeric environments (e.g., hydrogel dots), mimicking nature through the use of diverse microstructures within defined confinements. However, establishing complex hybrid structures to mimic biological processes and functions under continuous flow with optimal utilization of all components involved in the reaction process represents a significant scientific challenge. To achieve spatial, chemical, and temporal control for any microfluidic application, compartmentalization is required, as well as the unification of different sensitive compartments in the reaction chamber for the microfluidic flow design. This study presents a self-regulating microfluidic system fabricated by a sequential photostructuring process with an intermediate chemical process step to realize pH-sensitive hybrid structures for the fabrication of a microfluidic double chamber reactor for controlled enzymatic cascade reaction (ECR). The key point is the adaptation and retention of the function of pH-responsive horseradish peroxidase-loaded polymersomes in a microfluidic chip under continuous flow. ECR is successfully triggered and controlled by an interplay between glucose oxidase-converted glucose, the membrane state of pH-responsive polymersomes, and other parameters (e.g., flow rate and fluid composition). This study establishes a promising noninvasive regulatory platform for extended spatio-chemical control of current and future ECR and other cascade reaction systems.
微流控流动反应器能够在聚合物环境（如，水凝胶点）中实现敏感生物催化剂，通过在限定的范围内使用多样的微结构来模拟自然。然而，在连续流动条件下建立复杂的混合结构以模拟生物过程和功能，并对反应过程中涉及的所有组分进行最佳利用，是一项重大的科学挑战。对于任何微流控应用，要实现空间、化学和时间控制，都需要进行分隔，并且在反应腔室中统一不同的敏感隔室以进行微流控流动设计。本研究提出了一种通过顺序光结构化过程和中间化学工艺步骤制造的自调节微流控系统，以实现用于制造用于受控酶级联反应（ECR）的微流控双腔室反应器的pH敏感混合结构。关键在于在连续流动条件下，pH响应性负载辣根过氧化物酶的聚合物囊泡在微流控芯片中的功能适配和保留。葡萄糖氧化酶转化的葡萄糖、pH响应性聚合物囊泡的膜状态以及其他参数（如流速和流体组成）之间的相互作用成功触发并控制了ECR。本研究为当前及未来的ECR和其他级联反应系统的扩展空间化学控制建立了一个有前景的非侵入性调节平台。
