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

使用智能表面隔离两性离子聚合物控制生物微流体装置表面化学

• 批准号: 10193245
• 负责人: Ayse Asatekin
• 金额: $ 25.08万
• 依托单位: TUFTS UNIVERSITY MEDFORD
• 依托单位国家: 美国
• 财政年份: 2021
• 资助国家: 美国
• 起止时间: 2021-08-01 至 2023-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10193245
• 关键词: Adhesions; Adoption; Adsorption; Air; Antibodies; Antigens; Avidin; Binding; Binding Sites; Biological; Biomanufacturing; Biomedical Research; Biotin; Case Study; Cell Adhesion; Cell Culture Techniques; Cells; Chemistry; Complex; Devices; Drug Industry; Gases; Glass; Goals; Healthcare; Hydrophobicity; Industry; Knowledge; Manufacturer Name; Measures; Mediating; Methods; Microfluidic Microchips; Microfluidics; Modification; Optics; Patients; Performance; Permeability; Pharmaceutical Preparations; Polymers; Property; Proteins; Protocols documentation; Research; Research Personnel; Resistance; Sampling; Silicon; Structure; Surface; Technology; Tissues; Translating; Water; Work; aqueous; base; biomaterial compatibility; cell type; copolymer; cost; design; drug use screening; experimental study; flexibility; functional group; hydrophilicity; improved; macromolecule; mechanical properties; member; monomer; nanoscale; new technology; novel; organ on a chip; physical property; polydimethylsiloxane; prevent; segregation; small molecule; solute; stability testing; tissue culture; user-friendly

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.

抽象的 通过组织培养实验在生物医学研究中使用微流体设备 （片上的组织/器官）和生物学分离正在迅速增长。聚二甲基硅氧烷（PDMS） 由于其特征复制到纳米级，因此一直是微流体的最受欢迎的材料， 柔韧性，氧合的气体渗透性和低成本。然而，PDM的疏水性导致 大分子（例如蛋白质）和疏水化合物（例如II类药物）的吸附 设备表面。这种咖喱在“片上器官”和其他应用中用于药物筛查。 当前改善PDMS表面亲水性的技术涉及添加的处理步骤和/或DO 不会产生长期保持亲水性的表面。他们也不能简单地合并 功能组促进特定生物分子的结合并产生生物活性表面。这 阻碍其大规模的实施和采用。我们的长期目标是开发智能材料 提高生物机体的精度，鲁棒性和功能，同时保持其大规模 制造简单，便捷且高效。在此应用程序中，我们详细介绍了一种简单的技术来修改 PDM通过理性设计的智能聚合物，当设备制造过程中与PDMS混合时， 与水溶液接触时，赞助将表面分离到表面并创建<1 nm层 这可以防止有机和生物分子的非特异性吸附，但可以将其功能化以控制 给定应用程序的特定绑定。我们的方法与现有PDMS设备完全兼容 制造协议，没有任何其他处理步骤。为了实现这一直接目标，我们的目标 开发新颖的CP添加剂，以“添加智能共聚物来修饰PDMS表面” （SCAMP），特别是具有Zwitterionic（Zi）组的PDM的高度分支CPS（AIM 1），带有 添加介导特定结合的官能团（AIM 2）。我们将设计和合成几个 每个智能共聚物类的成员，准备与PDM的混合物中的样本，以及 根据它们的机械性能，光学清晰度，表面化学和趋势来表征它们 吸附蛋白和小分子药物。对于功能化样品，我们还将测量 选择性溶质（例如生物素功能表面上的Avidin）和细胞类型的选择性粘附。我们将 我们将准备 来自最有前途的候选人的微流体设备，并在长期细胞中验证其性能 培养实验。我们希望我们开发的技术可以改善微流体的可及性 通过提供低成本和用户友好的方法来最终用户（患者，研究人员，制药行业） 可靠的生物微流体的制造。