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

摘要 微流控装置在生物医学组织培养实验研究中的应用 （组织/芯片上器官）和生物分离正在迅速发展。聚二甲基硅氧烷（PDMS） 由于其特征复制到纳米级， 柔韧性好，透气性好，便于充氧，成本低。然而，PDMS的疏水性导致 吸附大分子（如蛋白质）和疏水化合物（如II和IV类药物） 设备表面。这限制了它在“器官芯片”和其他应用中的药物筛选。 改善PDMS表面亲水性的现有技术涉及增加的加工步骤和/或不 不会产生长时间保持亲水性的表面。它们也不能同时 官能团，以促进特定生物分子的结合并产生生物活性表面。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 提高生物微流体的精度、鲁棒性和功能性，同时保持其大规模 制造简单、容易且有效。在这个应用中，我们详细介绍了一种新颖的，简单的技术来修改 PDMS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 其防止有机和生物分子的非特异性吸附，还可以被功能化以控制 针对特定应用的特定绑定。我们的方法与现有的PDMS设备完全兼容 制造协议，而无需任何额外的处理步骤。为了实现这一目标，我们的目标是 开发新型CP添加剂，用于“智能共聚物添加剂用于PDMS表面改性” （SCAMPS），特别是具有两性离子（ZI）基团的PDMS的高度支化CP（Aim 1）， 添加介导特异性结合的官能团（目的2）。我们将设计并合成几种 每个智能共聚物类的成员，从它们与PDMS的共混物制备样品，以及 根据其机械性能、光学透明度、表面化学和趋势对其进行表征 吸附蛋白质和小分子药物。对于功能化样品，我们还将测量 所需溶质（例如生物素功能表面上的抗生物素蛋白）和细胞类型的选择性粘附。我们将 还可以测试在空气和水中长期储存后表面的稳定性和化学性质。我们将准备 微流控器件从最有前途的候选人，并验证其性能在长期的细胞 培养实验我们希望我们开发的技术能够提高微流体的可及性 通过提供低成本和用户友好的方法， 可靠的生物微流体的制造

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.