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 通过组织培养实验使用微流体装置进行生物医学研究 （组织/器官芯片）和生物分离正在快速增长。 由于其特征可复制到纳米级，因此成为微流体中最受欢迎的材料， 然而，PDMS 的疏水性导致了其灵活性、氧化透气性和低成本。 大分子（例如蛋白质）和疏水性（化合物例如 II 类和 IV 类药物）的吸附 这限制了其在“器官芯片”和其他应用中的药物筛选的用途。 当前提高 PDMS 表面亲水性的技术涉及增加加工步骤和/或 它们不能形成长期保持亲水性的表面，也不能同时结合。 促进特定生物分子结合并创建生物活性表面的官能团。 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、方便且高效 在此应用中，我们详细介绍了一种新颖、简单的修改技术。 PDMS 通过合理设计的智能聚合物在设备制造过程中与 PDMS 混合时， 与水溶液接触时自发分离到表面并形成 <1 nm 的层 防止有机分子和生物分子的非特异性吸附，但可以功能化以控制 我们的方法与现有的 PDMS 设备完全兼容。 为了实现这一近期目标，我们的目标是无需任何额外的处理步骤即可制造协议。 开发用于“PDMS 表面改性的智能共聚物添加”的新型 CP 添加剂 (SCAMPS)，特别是具有两性离子 (ZI) 基团的 PDMS 的高度支化 CP（目标 1）， 添加介导特异性结合的官能团（目标 2）。 每个智能共聚物类别的成员，从其与 PDMS 的混合物中制备样品，以及 根据机械性能、光学透明度、表面化学和趋势来表征它们 对于功能化样品，我们还将测量吸附蛋白质和小分子药物。 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。 还测试长期储存在空气和水中的表面稳定性和化学性质。 来自最有前途候选者的微流体装置并验证其在长期细胞中的性能 我们期望我们开发的技术能够提高微流体的可及性。 通过提供低成本且用户友好的方法来向最终用户（患者、研究人员、制药行业）提供 制造可靠的生物微流体。