Controlling biomicrofluidic device surface chemistry using smart surface-segregating zwitterionic polymers

摘要 微流控装置在组织培养实验生物医学研究中的应用 (芯片上的组织/器官)和生物分离正在迅速增长。聚二甲基硅氧烷(PDMS) 一直是最受欢迎的微流体材料，因为它的特征复制到纳米级， 弹性好，气体透氧性好，成本低。然而，PDMS的疏水性导致了 大分子(如蛋白质)和疏水化合物(如II类和IV类药物)在其上的吸附 设备表面。这限制了它在“芯片器官”和其他应用中进行药物筛选的使用。 目前提高PDMS表面亲水性的技术包括增加处理步骤和/或 不要创建长时间保持亲水性的表面。它们也不能同时合并 促进特定生物分子结合并产生生物活性表面的官能团。这 阻碍了它们的大规模实施和采用。我们的长期目标是开发智能材料 在保持其规模化的同时提高生物微流体的精密度、稳定性和功能性 制造简单、方便、高效。在本应用程序中，我们详细介绍了一种新的、简单的修改技术 通过合理设计的智能聚合物，当在设备制造过程中与PDMS混合时， 当与水溶液接触时，自发地分离到表面并产生1 nm的层 这防止了有机和生物分子的非特异性吸附，但可以官能化来控制 指定应用程序的特定绑定。我们的方法与现有的PDMS设备完全兼容 无需任何额外处理步骤即可制造协议。为了实现这一近期目标，我们的目标是 开发用于“PDMS表面改性的智能共聚添加剂”的新型CP助剂 (SCAMPS)，特别是具有两性离子(Zi)基团的PDMS的高度支化的CP(目标1)，具有 添加调节特定结合的官能团(目标2)。我们将设计和综合几个 每个智能共聚物类别的成员，从他们与PDMS的混合物中制备样品，以及 从机械性能、光学清晰度、表面化学和倾向性方面对它们进行表征 吸附蛋白质和小分子药物。对于功能化的样本，我们还将测量 所需溶质(例如生物素功能表面的亲和素)和细胞类型的选择性粘附性。我们会 还要测试在空气和水中长期储存时表面的稳定性和化学成分。我们会做好准备 最有希望的候选微流控器件及其在长期电池中的性能验证 培养实验。我们希望我们开发的技术能够改善微流体的可及性。 为最终用户(患者、研究人员、制药行业)提供一种低成本、用户友好的方法 制造可靠的生物微流体。

Abstract The use of microfluidic devices in biomedical research through tissue culture experiments (tissues/organs-on-chips) and biological separations is growing rapidly. Polydimethylsiloxane (PDMS) has been the most popular material for microfluidics due to its feature replication down to the nanoscale, flexibility, gas permeability for oxygenation, and low cost. Yet, the hydrophobicity of PDMS leads to the adsorption of macromolecules (e.g. proteins) and hydrophobic compounds (e.g. Class II & IV drugs) on device surfaces. This curtails its use for drug screening in “organs-on-chips”, and other applications. Current technologies to improve PDMS surface hydrophilicity involve added processing steps and/or do not create surfaces that remain hydrophilic for long periods. They also cannot simultaneously incorporate functional groups to promote binding of specific biomolecules and create bioactive surfaces. This hampers their large-scale implementation and adoption. Our long-term goal is to develop smart materials to improve the precision, robustness, and functionality of biomicrofluidics while keeping their large-scale fabrication simple, facile, and efficient. In this application, we detail a novel, simple technology to modify PDMS via rationally designed smart polymers that, when blended with PDMS during device manufacture, spontaneously segregate to surfaces and create a <1 nm layer when in contact with aqueous solutions that prevents non-specific adsorption of organic and biomolecules, yet can be functionalized to control specific binding for a given application. Our methods are fully compatible with existing PDMS device manufacture protocols without any additional processing steps. To achieve this immediate goal, we aim to develop novel CP additives for “Smart Copolymer Addition for Modification of PDMS Surfaces” (SCAMPS), specifically highly branched CPs of PDMS with zwitterionic (ZI) groups (Aim 1), with the addition of functional groups that mediate specific binding (Aim 2). We will design and synthesize several members of each smart copolymer class, prepare samples from their blends with PDMS, and characterize them in terms of their mechanical properties, optical clarity, surface chemistry, and tendency to adsorb proteins and small molecule drugs. For functionalized samples, we will also measure the selective adhesion of desired solutes (e.g. avidin on biotin-functional surfaces) and cell types. We will also test the stability and chemistry of the surface upon long-term storage in air and water. We will prepare microfluidic devices from most promising candidates and validate their performance in long-term cell culture experiments. We expect the technologies we develop to improve the accessibility of microfluidics to end users (patients, researchers, drug industry) by providing a low-cost and user-friendly approach to the fabrication of reliable biomicrofluidics.